Inhibitory effect of liposomes survivin antisense oligonucleotide on human hepatic carcinoma transplanted subcutaneously in nude mice

AIM: To explore the effects of liposomes survivin antisense oligonucleotides (ASODN) on growth of human hepatic carcinoma transplanted subcutaneously in nude mice. METHODS: Nude mouse model of human hepatic cancer was established by transplantation of hepatic cancer cell line SMMC-7721/ADM subcutaneously. Models were divided randomly into six groups: control group, liposome group, sense oligonucleotide (SODN) group, 200 μg/L, 400 μg/L and 600 μg/L ASODN groups. Different treatments were given respectively. Weight and volume of subcutaneous tumors were measured, and tumor growth inhibitory rate was calculated. Morphological changes of transplanted tumor cells were observed under light microscope. The expression of Survivin was detected by immunohistochemistry. RESULTS: The growth of tumors was significantly inhibits in all ASODN groups compared with control, liposome and SODN groups (P<0.05). Volume of subcutaneous tumors decreased in a time-dependent and dosage-dependent manner (P<0.5). CONCLUSION: Survivin ASODN inhibits the growth of human hepatic carcinoma in nude mice.     

Effect of curcumin on expression of p21 and CD44V6 in human breast cancer xenografts

AIM:To study the effect of curcumin on the expression of p21 and CD44V₆ in breast carcinoma in nude mice.METHODS:Nude mice were xenografted with human breast cancer cell line MCF-7 and randomly divided into 2 groups (n=4 in each group): control group and curcumin group. In latent period,the percentage of tumor development was observed. Tumors were measured and the surface areas were calculated. RT-PCR was performed to detect the expression level of cyclin D1,p21 and CD44V₆ mRNA. RESULTS:The tumor surface areas in the curcumin group were significantly lower than those in control group. In curcumin treatment group,the expression of p21 was up-regulated while cyclin D1 was nearly not changed. The expression of CD44V₆ was significantly down-regulated in curcumin group.CONCLUSION:Curcumin inhibits the expression of CD44V₆ and up-regulates the expression of p21 in nude mice bearing human breast cancer cell line MCF-7.     

Apoptosis of implanted tumor of human primary gastric cancer cells in nude mice induced by resveratrol

AIM: To investigate the molecular mechanism of the apoptosis of implanted tumor of human primary gastric cancer cells in nude mice induced by resveratrol. METHODS: Human primary gastric cancer cells were planted into nude mice to establish the cancer model. Resveratrol at different doses were injected near the carcinoma on the nude mice. After treatment, transmission electron microscope and TUNEL staining method were used to detect the apoptosis of implanted tumor cells. Immunohistochemical staining and RT-PCR were used to detect the expression of apoptosis-related genes bcl-2 and bax in implanted tumor. RESULTS: Resveratrol significantly inhibited carcinoma growth when it was injected near the carcinoma. The apoptotic cells in implanted tumor induced by resveratrol were detected by transmission electron microscope and TUNEL staining, immunohistochemical staining and RT-PCR showed resveratrol inhibited bcl-2 expression and increased bax expression in human primary gastric cancer cells. CONCLUSION: Resveratrol inhibits implanted tumor of human primary gastric cancer cells in nude mice through inducing apoptosis. This apoptosis may be mediated by down-regulation of bcl-2 expression and up-regulation of bax expression.     

Knockdown of RRM2 gene by siRNA inhibits human breast cancer cell proliferation,migration and tumor growth in nude mice

AIM: To explore the effect of ribonucleotide reductase M2 (RRM2) gene knockdown by siRNA on the proliferation and migration of human breast cancer MCF-7 cells and the tumor growth in BALB/c nude mice. METHODS: The mRNA and protein expression leves of RRM2 in human breast cancer cell line MCF-7 and human normal breast cell line MCF-10A were determined by real-time PCR and Western blotting. siRNA-RRM2 was constructed and transfected into MCF-7 cells at different time points and different concentrations. The silencing efficiency of RRM2 gene was detected by real-time PCR. The cell proliferation was measured by CCK-8 assay. The migration was observed using Transwell cell migration system. The effect of siRNA-RRM2 on the tumor growth was determined in nude mice. RESULTS: The mRNA and protein levels of RRM2 were higher in MCF-7 cells than those in MCF-10A cells. siRNA-RRM2 down-regulated the expression of RRM2 in MCF-7 cells in a time-and concentration-dependent manner. The results of CCK-8 assay showed that siRNA-RRM2 inhibited the proliferation ability of MCF-7 cells, but not that of MCF-10A cells. The results of Transwell assay indicated that siRNA-RRM2 inhibited the migration ability of MCF-7 cells. siRNA-RRM2 also inhibited the tumor growth in nude mice. CONCLUSION: RRM2 overexpression is associated with the breast cancer proliferation and migration. Suppression of RRM2 function is a potential therapeutic strategy for treating breast cancer.     

Effect of captopril on AGS nude mouse model of gastric cancer

AIM: To observe the effect of captopril on the genesis and development of gastric cancer, and to explore its clinical treatment feasibility for gastric cancer. METHODS: The human gastric cancer cell line AGS was used to establish a tumor model in nude mice, and the model mice were randomly divided into 3 groups: positive control (5-fluorouracil) group, normal control (saline) group and experimental (captopril) group. After intraperitoneal injection or intragastric administration of the drugs, the tumor growth curve was determined, and the tumor tissues were also sampled to detect the expression of Ki-67, STAT3, Bax and Bcl-2 by real-time quantitative PCR and immunohistochemistry. The apoptosis was detected by TUNEL+DAPI staining. RESULTS: The tumor growth curve showed that the tumor model in the nude mice was successfully established. The tumor volumes among groups showed significantly different after 14 d growth. The increase in the tumor volume in normal control group was significantly faster than that in the other two groups, and that in positive control group was the slowest. The expression of Bax in captopril group increased, and the expression of STAT3, Ki-67 and Bcl-2 was reduced as compared with normal control group and positive control group. Compared with normal control group, the apoptotic rate increased significantly, and the protein expression of p-STAT3 and STAT3 decreased obviously in positive control group and captopril group. CONCLUSION: With better feasibility, angiotensin-converting enzyme inhibitor captopril has a significant effect on treating gastric cancer in the AGS nude mouse model by regulating the expression of STAT3, Bax, Bcl-2 and Ki-67 to accelerate the apoptosis of cancer cells, thus inhibiting tumor growth.     

Inhibitory effect of survivin antisense oligodeoxyribonucleotide combined with DDP in nude mice bearing human osteosarcoma xenograft

AIM:To investigate the feasibility and its mechanisms of improving therapeutic effect by antisense gene therapy combined with chemotherapy in osteosarcoma. METHODS:The human osteosarcoma implanted tumor model in the nude mice was established. By intratumoral injection and abdominal cavity administration, the tumor bearing mice were treated with survivin ASODN in combination with diamminedichloroplatinum (DDP) for a week. Comparison with each single-agent therapy and control group was performed in aspects such as tumor growth condition, pathological changes of tumor tissues;survivin protein expression in tumor tissues by immunohistochemistry, survivin mRNA expression levels by RT-PCR method and tumor apoptosis by Tdt-mediated dUTP nick end labeling (TUNEL). RESULTS:All nude mice survived the therapy. As compared with the control group, the antisense gene therapy group presented synchronous decrease in survivin mRNA and protein expression;all therapy group displayed tumor growth inhibition and cell apoptosis with different extent;while in contrast to single-agent therapy group, the combined therapy group showed stronger inhibition of tumor growth and abundant tumor cell apoptosis with the highest apoptotic rate. CONCLUSION:Synergistic effect was achieved by combination of DDP with ASODN that may overcome drug resistant of DDP and the combined strategy may shed new light on the cancer therapy.     

Inhibitory effect of EGCG on proliferation and HIF-1α/VEGF expression in cell line HepG2

AIM: To study the molecular mechanism of EGCG on inhibiting the growth of hepatic carcinoma. METHODS: The proliferation of hepatic cell line HepG2 cultured with different doses of EGCG was studied by MTT and suspension/adherence methods. The effect of EGCG on the expression of HIF-1α/VEGF at mRNA and protein levels in vitro and in vivo was evaluated by RT-PCR and Western blotting, respectively. The inhibition of EGCG on the growth of tumor implanted into athymic nude mice was also observed. RESULTS: The proliferation of hepatic cell line HepG2 was inhibited by EGCG in a dose-dependent manner. The expression of HIF-1α/VEGF was suppressed markedly by EGCG at protein level. However, the inhibitory effect of EGCG on the mRNA expression was only observed on VEGF, not on HIF-1α. In the animal experiment, the implanted tumor growth was inhibited by 39.8%±5.1%. CONCLUSION: EGCG suppresses the hepatic carcinoma cell growth, and interrupts the HIF-1α/VEGF signaling pathway significantly, indicating a fundamental mechanism of EGCG for inhibiting tumor growth.     

A malignant transformation model of TERC-deficient 16HBE cells induced by MNNG

AIM: To establish a malignant transformed human bronchial epithelial (16HBE) cell model induced by N-methyl-N’-nitro-N-nitrosoguanidine (MNNG). METHODS: A combination plasmid expressing shRNA specific for the human telomerase RNA component (TERC) was transfected into 16HBE cells and G418-resistant stable clone was obtained, named 16HBE-1 cells. The mRNA expression of TERC in 16HBE-1 cells was detected by RT-PCR. 16HBE-1 cells were treated with MNNG at concentration of 1 mg/L for 1 h in every other generation for 27 times until the transforming foci were formed. The cells from the transforming foci were separated and called 16HBE-T cells. Malignancy of 16HBE-T cells was identified by colony formation in soft agar and tumorigenesis in nude mice. RESULTS: 16HBE-T cells grew in soft agar and turned into tumor in nude mice. The tumor was squamous carcinoma confirmed by histopathological examination. CONCLUSION: The malignant transformation of TERC-deficient 16HBE cells is successfully induced by MNNG.     

Effects of RNA interference of FABP5 on subcutaneous tumor of human hepatocellular carcinoma cell line HepG 2 transplanted in nude mice

AIM: To investigate the effect of recombinant lentiviral vector for RNA interference (RNAi) on the expression of fatty acid-binding protein 5 (FABP5) gene in hepatocellular carcinoma HepG2 cells and tumor formation in nude mice.METHODS: RNAi lentiviral vector was used in the experiment. Human hepatocellular carcinoma HepG2 cells were divided into 3 groups:the HepG2 cells in experimental group were transfected with the recombinant lentivirirus vector LV-shRNA-FABP5, the cells in negative control group were transfected with a control lentiviral vector LV-shRNA-NC, and the cells in normal control group were without any treatment. The nude mice were randomly divided into 3 groups. The growth of the transplanted tumor cells in the nude mice was observed. The tumor growth curve, volume and weight were determined 4 weeks after the cell inoculation. The expression of FABP5 was detected by real-time PCR, Western blot and immunohistochemical staining.RESULTS: Transfection of the lentiviral vector FABP5-shRNA obviously reduced FABP5 expression in the HepG2 cells. Tumor formation was all positive in the 3 groups of the nude mice inoculated with the tumor cells. Compared with normal control group and negative control group, the tumor growth slowed significantly in experimental group with smaller volume and weight. FABP5 expression in the transplanted tumor tissues was significantly down-regulated at mRNA and protein levels in experimental group as compared with normal control group and negative control group.CONCLUSION: RNAi-induced down-regulation of FABP5 effectively inhibits the growth of transplanted hepatocellular carcinoma, suggesting that FABP5 gene may be an effective target for gene therapy in treating liver cancer.     

Anti-angiogenesis effects of IFN-α on cultured HUVECs and human HCC bearing nude mouse

AIM:To evaluate the anti-angiogenesis effect of interferon-α (IFN-α) on cultured human umbilical vein endothelial cells(HUVECs) and human hepatocellular carcinoma (HCC) bearing nude mouse.METHODS:Anti-proliferation test,MTT test，tube-formation test,migration test on cultured HUVECs were employed and the tumor volume and microvascular desity (MVD) of IFN-α treated human hepatoma cell line (HuH7) were meassured. RESULTS:IFN-α displayed apparent inhibitory effects on cultured HUVECs in anti-proliferation test,MTT test,tube-formation test,migration test,and the tumor diameter and MVD in IFN-α treated HuH7 inoculated nude mouse group were significantly less than those in PBS treated HuH7 inoculated nude mouse group.CONCLUSION: IFN-α inhibits tumor growth through anti-angiogenesis.     

Anti-cancer effect of cytotoxic T lymphocytes activated by sensitized dendritic cells

AIM: To investigate the anti-cancer effect of cytotoxic T lymphocytes (CTL) activated by sensitized dendritic cells (DCs). METHODS: Immature DCs were induced in vitro from peripheral blood monocytic cells (PBMC) and sensitized by adding tumor cells antigen extract. DCs were identified by their morphology and surface markers. MTT assay was used to evaluate the killing activity of CTL activated by sensitized DCs. The effects of specific CTL cells on inhibiting transplanted tumor HT-29 growth and on preventing HT-29 tumor generation were evaluated by injecting CTL into nude mice. RESULTS: After cultured for seven days, a large number of activated DCs were obtained with typical morphology, extensive stimulatory proliferation capacity and high CD80 (63.5%), CD83 (67.6%) and CD3/HLA-DR (83.2%) expressions. The killing activity of CTL at 20∶1 ratio of effective cells to target cells was more than 75% to tumor cells, 35%-45% to homologous cell line and weaker to other germ cell line (P<0.01). Injection of CTLs activated by HT-29 cell antigen sensitized DCs inhibited HT-29 transplanted tumor growth and prevented HT-29 tumor occurring in nude mice (P<0.05). PCNA expression level in tumor cells in CTL therapy group was dramatically lower than that in control (P<0.05). CONCLUSION: CTL activated by sensitized DCs kill tumor cells specifically, inhibit transplanted tumor growth and prevent tumor transplantation in nude mice.     

Effect of HGF gene transfection on human lymphoma xenografts in nude mice

AIM：To explore the promotion effect of hepatocyte growth factor (HGF) gene transfection on human lymphoma xenografts in nude mice. METHODS：The model of human lymphoma xenograft in nude mice was established by transplantation of Raji cells, which were transfected with recombinant plasmid pVITRO2-HGF harboring the HGF gene. The body weight of the nude mice and the tumor size were dynamically monitored and the tumor tissues were obtained after 8 weeks. Additionally, the methods of terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) and immunohistochemistry were used to detect the apoptotic index (AI) and microvessel density (MVD). RESULTS：The success rate of the human lymphoma xenografts in nude mice was 96.7%. The tumor volume in HGF transfection group was significantly greater than that in HGF transfection+VP-16 group and control groups (non-transfection group and empty vector group). The tumor volume in HGF transfection+VP-16 group was also bigger than that in control groups. No difference of the tumor volume between non-transfection group and empty vector group was observed. AI in HGF transfection group was substantially lower than that in control groups. AI in HGF transfection+VP-16 group showed a little higher than that in HGF transfection group, yet was still lower than that in control groups. MVD in HGF transfection group was extraordinary higher than that in control groups, but decreased after VP-16 induction (P<0.01), which was still higher than that in control groups. CONCLUSION：HGF gene transfection significantly promotes the growth of human lymphoma xenografts in nude mice and substantially inhibits the apoptosis presumably owing to promoting tumor angiogenesis and inhibiting tumor cell apoptosis.     

The tumor-seeking specificity of [125I]-(A14)-insulin in human hepatoma bearing nude mice

AIM: To observe tumor-seeking specificity of [¹²⁵I]-(A14)-insulin in human hepatoma bearing nude mice. METHODS: The in vivo tissue distribution and inhibition studies of [¹²⁵I]-(A14)-insulin in human hepatoma bearing nude mice were performed. RESULTS: In the tissue distribution study, a significant accumulation of [¹²⁵I]-(A14)-insulin was observed in the tumor site of nude mice. The tumor/blood and tumor/muscle radioactive ratio gradually increased with lengthening time following injection of [¹²⁵I]-(A14)-insulin. The inhibition ratio in the tumor tissue of nude mice in the inhibition study was 35.0%. CONCLUSION: There is a specific uptake of [¹²⁵I]-(A14)-insulin through receptor-mediated process in the hepatoma tissue of nude mice.     

Effects of STK15 overexpression on growth of human esophageal carcinoma cell line KYSE150

AIM:To investigate the effects of serine/threonine kinase 15 (STK15) overexpression on the growth of human esophageal squamous-cell carcinoma (ESCC) cell line KYSE150. METHODS:Recombinant pEGFP-C1-STK15 expression vector was transfected into KYSE150 cells using LipofectamineTM 2000 and the expression of STK15 was detected by fluorescence microscopy and Western blotting. The proliferation of the cells in vitro was measured by MTT assay. The cell cycle distribution and apoptosis were detected by flow cytometry. The proliferation of the cells in vivo was measured by tumorigenicity experiment in nude mice. RESULTS:After recombinant pEGFP-C1-STK15 expression vector was stably transfected into KYSE150 cells, GFP-STK15 fusion protein localized to centrosome and spindle. The STK15-overexpressing colonies were further confirmed by Western blotting. MTT assay showed that the proliferation of the cells in STK15 overexpression group was increased compared with control group (P<0.01). Flow cytometry analysis showed that the percentage of the cells in G0/G1 phase and the cell apoptosis in STK15 overexpression group were decreased compared with control group (P<0.01). The tumorigenicity experiment in nude mice showed that the proliferation of the cells in STK15 overexpression group was increased compared with control group (P<0.01). CONCLUSION: Overexpression of STK15 in human ESCC KYSE150 cells promotes the cell growth in vitro and in vivo, indicating that STK15 may serve as a novel therapeutic target for esophageal carcinoma.     

Establishment of human pancreatic tumor xenograft mouse model for evaluating tumor-homing and gene-silencing effects of siRNA-loading nanoparticles

AIM：To establish an effective and rapid method to develop transplanted subcutaneous pancreatic carcinoma by inducing PANC-1 cells into nude mice, and then use this mouse model to evaluate the tumor-homing and gene-silencing effects of siRNA-loading nanoparticles in vivo. METHODS：Different numbers of PANC-1 cells in 100 μL or 300 μL PBS were inoculated subcutaneously into the right flank of BALB/c (nu/nu) mice. When the tumor volume reached 100 mm3, siRNACY5.5 nanoparticles were injected through the mouse tail vein to perform in vivo imaging assay. Besides, the mice were randomly divided into 3 treatment groups treated with PBS, scrambled control RNA nanoparticles and siKras nanoparticles, respectively. The protein expression of Kras was detected by Western blotting and immunohistochemical staining. RESULTS：After inoculated with 1×107 PANC-1 cells in 300 μL PBS, all mice developed tumors within 2 weeks. The in vivo results showed that siRNA-loading nanoparticles accumulated in the tumor tissues and exerted gene silencing effect. CONCLUSION:In the present study, an effective and rapid method was established for PANC-1 cells to induce transplanted subcutaneous pancreatic carcinoma in nude mice within 2 weeks, which is suitable for in vivo imaging and treatment evaluations as a reproducible and reliable way for the further experiments.     

Inhibition of survivin expression in BGC-823 cells by RNA interference

AIM: To investigate the feasibility and specificity of gastric carcinoma gene therapy by utilizing RNA interference (RNAi) to inhibit survivin expression in vitro and in vivo. METHODS: Small interference RNA (siRNA) homologous to survivin was designed. pTZU6+1-siRNA-survivin vector was constructed and transfected into BGC-823 cells. The transplanted BGC-823 tumor in nude mice was established to induce RNAi. The changes of survivin gene expression, tumor cell cycle and cell apoptosis were detected by flow cytometry, RT-PCR, Western blotting, immunochemistry and TUNEL. RESULTS: The expression of survivin was obviously inhibited by RNAi in vitro. The phase of cell cycle indicated the reduction of S phase, while G1/G0 phase increased. Cell apoptosis was obvious. Both the mRNA level and the protein expression of survivin decreased obviously. The tumor size reduced after treated with pTZU6+1-siRNA-survivin vector in vivo. The expression of survivin decreased in siRNA treatment group. In contrast, little change in control group in vitro and in vivo was observed. CONCLUSION: RNA interference down-regulates survivin gene expression, inhibits BGC-823 cell proliferation and induces cell apoptosis with good specificity, which may be a possible new approach for neoplasm gene therapy.     

NFATc1 promotes vascular generation of epithelial ovarian cancer transplanted tumor by regulating CXCR2, FGF-2 and PDGF-BB

AIM: To investigate the role of NFATc1 in vascular generation in the nude mice transplanted with human ovarian cancer SKOV3 cells. METHODS: NFATc1 expression was silenced by siRNA in SKOV3 cells. Human ovarian cancer transplantation nude mouse model was established by transplanting with SKOV3 cells in which the NFATc1 gene was silenced by siRNA technique. The expression of NFATc1, CXCR2, FGF-2 and PDGF-BB at mRNA and protein levels was determined by RT-PCR, Western blotting and immunohistochemical staining. The tumor growth, angiogenesis and lymphangiogenesis were also observed. RESULTS: Over-expression of NFATc1 was observed in human ovarian cancer tissues. The silencing of NFATc1 expression by siRNA decreased tumorigenesis of transplanted ovarian cancer cells in the nude mice, reduced tumor vascular generation and inhibited the expression of CXCR2, FGF-2 and PDGF-BB at mRNA and protein levels. CONCLUSION: NFATc1 is overexpressed in ovarian cancer. NFATc1 silencing regulates the tumor vascular generation. NFATc1 thus has potential as a therapeutic target and for use in the diagnosis and evaluating prognosis of epithelial ovarian cancer.     

Inhibitory effects of LDL-ACM complex on subcutaneous implanted tumors in nude mice()

AIM: In order to evaluate the applicable value of LDL as a targeted vehicle for chemotherapeutic agents, we investigated and compared the inhibitory effects of LDL-ACM complex and free ACM on nude mice's subcutaneous implanted tumors derived from gastric cancer cell lines, SGC-7901 and NKM-45. METHODS: LDL-ACM complex was prepared and the tumor model of nude mice was established by subcutaneous implantation of SGC-7901 and NKM-45. Then, the groups of nude mice developed subcutaneous implanted tumors were received either LDL-ACM complex or free ACM. Subsequently, the tumor size, weight and leukemia cell counts were measured and the rates of tumor-inhibition and the survival were compared among the groups. RESULTS: The inhibitory effects of LDL-ACM complex on the tumors, especially on SGC-7901 implanted tumors were much more obvious than that of free ACM. It was also indicated that the action of LDL-ACM complex was mediated by LDL receptor. CONCLUSION: These results showed that LDL-ACM complex had significant inhibitory effects on the implanted tumors and the effect might be mediated by LDL receptor.     

Chutan-Jiedu decoction reverses resistance of lung cancer to gefitinib by processing EMT

AIM: To investigate the mechanism of Chutan-Jiedu decoction (CJD) reversing the resistance of lung cancer to gefitinib via epithelial-mesenchymal transition (EMT) pathway.METHODS: BALB/c nude mice (n=60) were selected to establish lung cancer xenograft model with human lung adenocarcinoma drug-resistant cell line H1975, which were randomly divided into 6 groups (10 mice per group):model group, gefitinib (0.04 g/kg) group, low-dose (13.52 g/kg) CJD group, middle-dose (27.04 g/kg) CJD group, high-dose (54.08 g/kg) CJD group, and combined medication group (27.04 g/kg CJD+0.04 g/kg gefitinib). The mice in each group were treated for 2 weeks before the tumor size and tumor weight were detected for the calculation of the tumor inhibitory rate. The mRNA and protein expression levels of E-cadherin, Snail and vimentin were determined by immunohistochemistry, Western blot and real-time PCR.RESULTS: Compared with model group and gefitinib group, the tumor size and the tumor weight in middle-dose CJD group, high-dose CJD group and combined medication group were decreased significantly (P<0.05). The results of immunohistochemistry, Western blot and real-time PCR showed that the expression of E-cadherin at mRNA and protein levels was increased significantly, while the expression of Snail and vimentin at mRNA and protein levels was decreased significantly (P<0.05).CONCLUSION: The growth of lung adenocarcinoma H1975 xenografts in nude mice is inhibited by CJD. In addition, the resistance of lung cancer to gefitinib is reversed. The mechanism may be related to the regulation of EMT-related protein expression.     

miR-509 regulates growth,invasion and migration of human hepatocellular carcinoma LM3 cells and survival of nude mice

AIM: To investigate the effect of microRNA-509 (miR-509) on the growth, invasion and migration of human hepatocellular carcinoma (HCC) LM3 cells and survival of tumor-bearing nude mice. METHODS: LM3 cells were transferred with miR-509 mimic and pcDNA Ras-related C3 botulinum toxin substrate 1 (pcRac1), and the expression of Rac1 was measured by Western blot. The relationship between miR-509 and Rac1 was determined by luciferase reporter assay. The invasion ability was determined by Transwell assay, and the migration ability was measured by wound healing assay. Xenograft model of HCC was established by subcutaneous injection with LM3 cells into nude mice. The survival rate of the mice were recorded and the protein level of Rac1 was determined by Western blot. RESULTS: miR-509 mimic inhibited the expression of Rac1 in the LM3 cells (P<0.05). pcRac1 attenuated the effect of miR-509 on Rac1. miR-509 also alleviated luciferase activity of wild Rac1 (P<0.05). Meanwhile, miR-509 mimic decreased the number of invasive LM3 cells and inhibited the migration of LM3 cells (P<0.05). In addition, over-expression of miR-509 up-regulated survival rate of model mice and decreased the protein level of Rac1 in the tumor tissue (P<0.01). CONCLUSION: miR-509 inhibits the invasion and migration of HCC cells and promotes the survival of tumor-bearing nude mice through inhibiting the expression of Rac1.