Relationship between activity of matrix metalloproteinases-2 and invasion,metastasis of breast cancer

AIM: To investigate relationship between activity of matrix metalloproteinases-2 (MMP-2, 72 kD) and invasion, metastasis of breast cancer. METHODS: Useing zymography and computer software assisted analysis, the activitive levels of MMP-2 (72 kD) in tissues from breast cancer were measeured. RESULTS: Mean activitive levels of MMP-2 72 kD (13.93±3.60) in breast cancer were lower than those in benign disease (21.43±8.31), P<0.05. There was no difference (P>0.05) in MMP-2 62 kD+72 kD of benign and malignant disease, but MMP-2 62 kD (13.83±4.53) and MMP-2 62 kD/62 kD+72 kD(0.48) respectively were significantly higher in malignant disease (P<0.01). It was also found that MMP-2 62 kD/62 kD+72 kD were apparently higher in invasive carcinomas (0.48) and lymph node metastases (0.61), P<0.01, respectively. CONCLUSION: These results demonstrated that a clear relationship between MMP-2 activity and the invasion and metastasis of breast carcinoma.     

Relationship between expression of somatostatin and DNA ploidy in breast cancer

AIM: To investigate the relationship between somatostatin and the pathologic type, estrogen receptor,DNA ploidy of nuclei in tumor cells of breast cancer.METHODS: 67 cases of primary breast cancer and 25 cases of benign breast tumor were examined by immunohistochemical stretomyces avidin peroxidase method. 26 cases of breast cancer selected at random were analyzed by flow cytometry.RESULTS: Somatostatin expressed significantly higher in low malignant breast cancer than that in high malignant breast cancer (P<0.05). Most of cancers with positive staining of somatostatin were diploidy,most of cancers with negative staining were aneuploidy,there had significant difference between two groups (P<0.05).CONCLUSION: Somatostatin may delay the progress of breast cancer,and somatostatin levels in cancer tissues may become a useful indicator for assessing prognosis of patients with breast cancer.     

Relationship between apoptosis,proliferation and expression,mutation of related genes in breast cancer

AIM:To study the relationship between apoptosis, proliferation and expression,mutation of related genes in breast cancer.METHODS:Methods of TUNEL, immunohistochemical S-P and PCR-SSCP were used respectively to study apoptotic index (AI), mitotic index(MI), expression of Bcl-2,p53,c-erbB-2,PCNA,Ki67,TopoⅡ and mutation of p53 in 54 cases of breast cancer.RESULTS:AI and MI were 9.40±3.78 and 5.96±2.36, respectively. There was a significant direct correlation between them(r=0.46.P＜0.01).High expression of Bcl-2,PCNA,Ki67,TopoⅡ coincided with high AI,MI(P＜0.01). High expression of p53,c-erbB-2 and mutation of p53 coincided with high MI(P＜0.01). Type of p53 mutation coincided with AI(P＜0.05).CONCLUSION:Disturbance of gene control between apoptosis and proliferation is related with expression,mutation of related genes in breast cancer.     

Relationship between zinc and zinc transporter expression in breast cancer MCF-7 cells

AIM: To study the changes of zinc transporter gene expression in MCF-7 cell line exposed to ZnCl₂ and TPEN. METHODS: Human breast cancer cell line MCF-7 was exposed to different concentrations of ZnCl₂ (0, 50, 100, 150, 200 μmol/L) and TPEN (0, 5, 10, 15 μmol/L), respectively. Twelve hours later, the cell viability was measured by MTT and levels of zinc transporter mRNA by RT-PCR. Zinquin was used to estimate the intracellular zinc concentrations. RESULTS: MCF-7 cells viability rate was significantly decreased when exposed to ZnCl₂ (with 150 μmol/L and 200 μmol/L) and TPEN. The intracellular zinc concentration was significantly increased when exposed to ZnCl₂ and decreased when exposed to TPEN. ZnT-1 mRNA level was increased along with the increasing concentration of ZnCl₂ but decreased when exposed to TPEN. The expressions of ZIP2 and ZIP10 were increased along with the increasing concentration of TPEN. CONCLUSION: ZnT-1 gene expression is induced by zinc supplement and repressed by zinc deficiency. ZIP2 and ZIP10 gene expressions are induced by zinc deficiency.     

Relationship of p21WAF1 gene polymorphisms with protein expression in breast carcinomas

AIM: To investigate the relationship between p21^WAF1gene polymorphisms and protein expression in breast carcinoma. METHODS: Polymerase chain reaction single-strand conformation polymorphisms technique (PCR-SSCP) and immunohistochemical assay of S-P immunostaining technique were used to study polymorphisms of p21^WAF1 and protein expression respectively on the specimen of paraffin-embedded tissues in 100 cases of breast carcinomas and 40 benign breast diseases as control. RESULTS: Two p21^WAF1 gene polymorphisms were found in 18% (18/100) of breast carcinomas and 5% (2/40) of control samples. The difference between the two groups was statistically significant (χ²=3.94, P＜0.05). The positive immunohistochemical reaction of p21^WAF1 protein were found in 50% (50/100) of breast carcinomas and 12.5% (5/40) of control samples. The difference between the two groups was statistically significant (χ²=16.84, P＜0.01). The positive immunohistochemical reaction of p21^WAF1 protein were found in 100% (18/18) of breast carcinomas with p21^WAF1 gene polymorphisms and 39% (32/82) of no p21^WAF1 gene polymorphisms. The difference between two groups was statistically significant (χ²=21.95, P＜0.01). The p21^WAF1 gene polymorphisms were correlated with the protein expression in breast carcinomas (r=0.576, P＜0.01). CONCLUSION: p21^WAF1 gene polymorphisms may create the different copies of mRNA and may make relevant protein molecules.     

Nucleostemin gene expression in human breast tumor tissues and its relation with clinical pathology

AIM: To study the expression of nucleostemin (NS) gene in human breast tumor tissues and the relations of NS gene expression level with histological grades,histological types and TNM stages of the tumor.METHODS: Total RNA was isolated from human breast tumor tissue.The methods of electrophoresis and RT-PCR were used in measuring NS gene expression level,and the relations of NS gene expression level with histological grades,histological types and TNM stages of the tumor were analyzed.RESULTS: The results indicated that there was no NS gene expression detected in normal breast tissues,and NS gene expression in malignant breast tumor tissues (P<0.01) was higher than that in the benign breast tumor tissues.The higher histological grades of the breast cancer showed the stronger NS gene expression (P<0.01),the higher TNM stages of the breast cancer showed the stronger NS gene expression (P<0.01),and the level of NS gene expression had not correlation with the histological types (P>0.05).CONCLUSION: It is suggested that there is no relation of NS gene expression level with histological types of the breast cancer,but there is a marked correlation of NS gene expression level with the histological grades and TNM stages.     

Relationship between genetic instability of nm23H1 gene and clinical pathological behaviors in gastric cancer and colonic cancer

AIM: To study the relationship between genetic instability of nm23H1 gene and clinical pathological behaviors in Chinese with gastric cancer and colonic cancer, and provide experimental basis for the mechanism of nm23H1 gene and tumor metastasis. METHODS: This study was conducted on 40 gastric carcinomas and 30 colonic carcinomas. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, PCR-SSCP, ordinary silver stain were used to study microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1 protein. RESULTS: In both gastric cancer and colonic cancer, the frequency of MSI was higher in TNM stageⅠandⅡthan that in stage Ⅲ and Ⅳ, while LOH was just opposite. Moreover, the frequency of LOH in lymph node metastasis cases was significantly higher than that without lymph node metastasis cases. The positive frequency of nm23H1 protein with lymph node metastasis was lower than that without lymph node metastasis cases. TNM stage III and IV also exhibited lower nm23H1 protein positive frequency compared with stage I and II. CONCLUSION: MSI and LOH can control the carcinogenesis and metastasis of gastric cancer and colonic cancer through different approaches. MSI may be an early period molecule marker of gastric cancer and colonic cancer. In contrast, LOH appears mostly in the late period of gastric cancer and colon cancer, indicating a high aggressive and poor prognosis.     

Study on genetic instability of nm23-H1 gene and expression of hMLH1,hMSH2 in sporadic gallbladder carcinoma

AIM: To examine the MSI and LOH of locus D17S396 and their influence on the expression of nm23-H1 in gallbladder tumors,and to examine the protein expression of hMLH1/hMSH2,which may provide experimental evidence for the tumor occurrence and metastasis.METHODS: Techniques such as DNA extraction,CR-SSCP,ordinary silver stain were used to study MSI and LOH of locus D17S396.Envision IHC was used to assess the expression of nm23-H1 and hMLH1/hMSH2.RESULTS: ① The frequency of heredity instability of gallbladder carcinoma was 42.55%.The frequency of LOH in liver and lymph node metastasis cases and in stage Nevin IV and V was significantly higher than that without metastasis and stage I,II and III.However,the frequency of MSI showed contrary correlation with some clinicopathologic characteristics.② The expression of nm23-H1 was 46.81%.The case with lymph node metastasis and Nevin stage IV and V showed significantly lower expression than that without lymph node metastasis and stage I,II and III.③ The expressions of hMLH1 and hMSH2 were 51.06% and 42.55% respectively.hMLH1 in lymph node and liver metastasis cases and in stage Nevin IV and V were significantly lower than that without metastasis and in stage I,II and III.④ Positive frequency of hMLH1 in MSI positive group was higher than that in MSI negative group.The positive frequency of nm23-H1 and hMSH2 protein in LOH positive group was lower than that in negative group.CONCLUSION: The heredity instability of nm23-H1 gene may be implicated pathogenesis and progression of gallbladder carcinoma.Both MSI and LOH of nm23-H1 control the development of gallbladder carcinoma independently in different paths.Abnormal expression of hMLH1/hMSH2 may be a molecule marker in early stage of gallbladder carcinoma.     

Survivin-2B induces apoptosis of human breast cancer cells

AIM：To explore the role of survivin-2B in the process of tumor cell apoptosis. METHODS：The survivin-2B gene was cloned into pcDNA3.1 vector and the recombinant plasmid pcDNA3.1-survivin-2B was obtained. Human breast cancer MCF7 cells were transfected with pcDNA3.1 and pcDNA3.1-survivin-2B using Lipofectamine 2000. The cell cycle was determined by propidium iodide staining, and the apoptosis was detected by annexin V/7-AAD staining 48 h after transfection. Meanwhile, tatal RNA was extrated and multiplex polymerase chain reaction based on GenomeLab GeXP Genetic Analysis System was performed to detect the expression of 21 tumor-related genes. RESULTS：Flow cytometry analysis indicated that over-expression of survivin-2B promoted the apoptosis and cell cycle arrest of MCF7 cells. Compared with control group, totally 10 differential expressed genes were related to the over-expressed survivin-2B, among which 2 were up-regulated and 8 were down-regulated. The expression of aldehyde dehydrogenase 4 family member A1 (ALDH4A1) was 48% down-regulated, and the expression of protein regulator of cytokinesis 1 (PRC1) was 1.08 folds up-regulated. CONCLUSION：Survivin-2B induces the expression changes of some tumor-related genes, which results in the apoptosis and G2/M arrest of MCF7 cells.     

Prognostic significance of FOXA1 and BRCA1 expression in triple negative breast cancer

AIM: To investigate the expression of forkhead box protein A1(FOXA1) BRCA1 protein,P53 and vascular endothelial growth factor (VEGF) in triple negative breast cancer (TNBC) and non-TNBC, and the relevance with the clinicopathological parameters for evaluating the prognosis. METHODS: The tumor samples were collected from 113 cases of breast cancer patients in the First Affiliated Hospital of Jinan University,and divided into TNBC group, luminal subtype group and HER-2 overexpression subtype group by the immunohistochemical results of estrogen receptor, progesterone receptor and HER-2. EnVision two-step method was used to detect the expression of FOXA1, BRCA1, P53 and VEGF in the tumor samples. RESULTS: Total FOXA1 positive expression rate was 63.7% (72/113), with 45.2% (19/42) in TNBC, 88.0% (44/50) in luminal subtype and 42.9% (9/21) in HER-2 overexpression subtype.The statistically sigfnificant difference among the 3 groups was observed (P<0.01). Total BRCA-1 positive expression rate was 47.8% (54/113), with 66.7% (28/42) in TNBC, 44.0% (22/50) in luminal subtype and 19.0% (4/21) in HER-2 overexpression subtype.The statisticallysignificant difference among the 3 groups was also observed (P<0.01). In the cases of clinical stages Ⅰ~Ⅱand histological grades 1~2, FOXA1 positive rate was higher than the FOXA1 negative rate (P<0.01). Negative correlations between FOXA1 positive rate and expression of P53/VEGF, and between FOXA1 positive rate and the recurrence rate were found (P<0.05). In the cases of clinical stages Ⅱ~Ⅲ and histological grades 2~3, the BRCA1 positive rate was higher than the BRCA1 negative rate (P<0.05). Positive correlations between BRCA-1 positive rate and the expression of P53/VEGF, and between BRCA1 positive rate and the recurrence rate were also observed (P<0.05). CONCLUSION: Expression of FOXA1 and BRCA1 in breast cancer is different. BRCA1 may be an adverse prognostic indicator for triple negative breast cancer.     

Role of VEGF-C in lymphangiogenesis and lymphatic metastasis of breast cancer

AIM: To study the inhibitory effect of VEGF-C/Flt-4 system on lymphangiogenesis and lymphatic metastasis of breast cancer. METHODS: Lymphatic endothelial cells (LEC) were cultured in vitro, the effects of VEGF-C and anti-Flt-4 antibody on the proliferation of treated cells were observed. The antisense oligodeoxynucleotides (ASODN) targeting VEGF-C was designed and its effect on VEGF-C gene expression in vitro experiments was observed. The nude mice transplantation tumor model was made and the effects of VEGF-C ASODN on lymphangiogenesis and metastasis in the model were determined. RESULTS: The supernatant of cultured PC3 cells promoted LEC proliferation obviously while the cells treated with anti-Flt-4 antibody were obviously decreased whenever cell counting. The mRNA and protein expression of VEGF-C in MCF-7 cells treated with ASODN were significantly lower than that in control groups in vitro. In vivo ASODN also significantly reduced the VEGF-C mRNA expression detected by RT-PCR. The result of 5-Nase-ALPase enzyme -histochemistry showed that ASODN had obvious inhibitory effect on tumor lymphangiogenesis. Tumor growth velocity in ASODN group was much slower than that in control group. ASODN also inhibited tumor volume and lymphatic metastasis. CONCLUSION: The strong relationships between VEGF-C/Flt-4 system and lymphangiogenesis and lymphatic metastasis of breast cancer have been observed. If the expression of Flt-4 is blocked, the proliferation of LEC induced by tumor cells can be blocked in some degree. ASODN inhibits tumor lymphangiogenesis and lymphatic metastasis by down-regulating VEGF-C expressions.     

Relationship between UGT1A1 gene polymorphisms and toxicity/efficacy of irinotecan-based chemotherapy in metastatic colorectal cancer

AIM: To investigate the correlation of UGT1A1 ^*28 and UGT1A1 ^*6 gene polymorphisms with irinotecan-associated adverse events and efficacy in the patients with metastatic colorectal cancer (mCRC) treated with irinotecan-based chemotherapy. METHODS: Analysis of UGT1A1 ^*28 and UGT1A1 ^*6 gene polymorphisms was performed in 207 gastrointestinal cancer patients admitted to our hospital from April 2010 to March 2012 by amplifying the gene fragments using PCR and direct sequencing. Fifty six cases with mCRC treated with irinotecan were chosen to observe the adverse events and efficacy during chemotherapy, and the time to progression (TTP) was also recorded. The incidence of different genotypes was compared. RESULTS: The distribution of the genotypes in 207 gastrointestinal cancer patients was as follows: UGT1A1 ^*28 wild-type (WT) genotype TA6/6 (164, 79.2%), heterozygous genotype TA6/7 (41, 19.8%), and homozygous genotype TA7/7 (2, 1.0%); UGT1A1 ^*6 WT genotype G/G (154, 74.4%), heterozygous genotype G/A (51, 24.6%), and homozygous genotype A/A (2, 1.0%). In the 56 mCRC cases, the incidence of grade 3 and 4 delayed diarrhea and neutropenia in the patients carrying UGT1A1 ^*6 (G/A and A/A) was higher than that in the WT genotype (6/6) (38.9% vs 7.9%,61.1% vs 29.0%, both P<0.05). The incidence of grade 3 and 4 thrombocytopenia in the patients carrying UGT1A1 ^*28 (TA6/7 and TA7/7) was higher than that in the WT genotype (TA6/6) (33.3% vs 2.1%, P<0.05). No significant difference of TTP and chemotherapeutic effect was observed between different genotypes. CONCLUSION: The UGT1A1 ^*6 (G/A and A/A) genotypes increase the risk of grade 3 and 4 delayed diarrhea and neutropenia, and the UGT1A1 ^*28 (TA6/7 and TA7/7) genotypes increase the risk of grade 3 and 4 thrombocytopenia in mCRC patients treated with irinotecan-based chemotherapy.     

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.     

Changes of MDR1 and MRP gene expression in primary breast cancer after neoadjuvant chemotherapy

AIM: To investigate the expression of drug resistance genes, MDR1 and MRP, in patients with primary breast cancer after neoadjuvant chemotherapy. METHODS: MDR1 and MRP gene expression were detected by semi-quantitative RT-PCR in 20 patients with primary breast cancer before and after chemotherapy. RESULTS: Before chemotherapy, MDR1 and MRPexpression could be detected in 15 cases (75%) and 18 cases (90%), respectively. After chemotherapy, expression of MDR1 was not significantly different from that before chemotherapy, but expression of MRPwas significantly different from that before chemotherapy. CONCLUSION: Drug resistance gene MRP, but not MDR1 expression is enhanced in patients with primary breast cancer subjected to neoadjuvant chemotherapy.     

Relationship between RUNX3,cyclin E,P21 and survival in gastric cancer patients

AIM:To evaluate the relationship between RUNX3,cyclin E,P21,biological features and survival in gastric cancer patients.METHODS:RUNX3 was examined using immunohistochemical staining.Cyclin E and P21 were analyzed by flow cytometry.Survival was evaluated by Kaplan-Meier survival curves.RESULTS:The positive-expression rate of RUNX3,cyclin E and P21 in tumor tissue from 56 patients with gastric cancer were 44.6%,64.3% and 32.1%,respectively.RUNX3 expression was correlated with lymph node metastasis and distant metastasis (P<0.05).Cyclin E might be related to depth of invasion,lymph node metastasis and distant metastasis (P<0.05).P21 was correlated with lymph node metastasis (P<0.05).It was revealed that RUNX3 and P21 were correlated (r=0.57,P<0.05),no correlation between RUNX3 and cyclin E was observed (r=0.25,P>0.05).Using Kaplan-Meier survival curves and the Log-rank test,there was correlation between RUNX3,cyclin E and survival (P<0.05).No correlation between P21 and survival was observed (P>0.05).CONCLUSION:RUNX3 may be related with tumorigenesis and tumor progression by affecting P21 expression.The detection of RUNX3 and cyclin E may be helpful in evaluating the clinicopathological parameters and prognosis in gastric carcinoma patients.     

Effects of furin inhibitor on metastasis of human breast cancer MCF-7 cells

AIM：To investigate the mechanism underlying breast cancer metastasis and to provide theoretical data for studying the pathogenesis of breast cancer onset and development. METHODS：Human breast cancer MCF-7 cells were treated with different concentrations of furin inhibitor α1-PDX for 48 h. Wound healing assay and Transwell assay were applied to detect the migration and invasion abilities of the MCF-7 cells. The expression of cell migration-associated proteins, including membrane-type 1 matrix metalloproteinase (MT1-MMP), vascular endothelial growth factor (VEGF)-C and VEGF-D, was determined by Western blotting. The protein levels of MMP2 and MMP9 in the supernatant were measured by ELISA. RESULTS：Compared with control group, 200 nmol/L of furin inhibitor exerted significant inhibitory effects on the cell migration (P<0.05). The expression of cell migration-associated proteins MT1-MMP, VEGF-C and VEGF-D was significantly inhibited after treated with α1-PDX (P<0.05). Significant inhibitory effects of α1-PDX on the expression of MMP9 and MMP2 (P<0.05) in the supernatant were observed. CONCLUSION：Furin inhibitor suppresses the metastasis of MCF-7 cells via down-regulating the expression of MMPs and VEGFs.     

Study on mutation of mitochondrial gene from rat breast cancer

AIM: To know the variations of the cytochrome b gene in cancer tissue, paracarinoma tissue and normal tissue and to inquire into the relationship between mutations of mitochondrial genome and carcinogenesis. METHODS: Cellular total DNA was extracted.The cytochrome b genes of three tissues were amplifyed with polymerase chain reaction(PCR). PCR products were analysed by DNA auto-sequencing method. RESULTS: The cytochrome b gene of cancer tissue had the C to G mutation at nt 14931, the C to G mutation at nt 15004 and the T to C mutation at nt15435,respectively. The cytochrome b gene of paracarinoma tissue had the A to C mutation at nt 15436. The cytochrome b gene of normal tissue had not mutation. CONCLUSION:Mitochondrial DNA mutations could be the endogenous factors that induce nuclear genome mutation. It could promoto carcinogenesis. The paracarinoma tissue was abnormal in DNA molecular level.     

Relationship between tumor metastasis suppressor gene KAI1 and the invasive and metastatic characteristics of osteosarcoma

AIM:To study the expression of metastasis suppressor gene KAI1 mRNA in osteosarcoma tissue and osteosarcoma cell lines,and the relationship between it and the biological behavior of the tumor cells.METHODS:RT-PCR was used to detect KAI1 mRNA in 18 cases of resected fresh osteosarcoma samples and three cultured osteosarcoma cell lines.The proliferative rate,the adhesive and invasive abilities of the 3 cell lines were detected.The results were treated by analysis system of images and analyzed with t test.RESULTS:The relative amount of KAI1 mRNA in osteosarcomas with lung metastasis was 0.80±0.50,while that was 1.48±0.64 in osteosarcomas without lung metastasis,the former was significantly lower than the latter (P<0.05).However,KAI1 mRNA had no corelation with the recurrence of osteosarcoma.The expression of KAI1 mRNA in U2-OS was highest (P<0.05),while the proliferation rate,the adhesive and invasive ability of U2-OS were the lowest among the 3 cell lines (P<0.01).CONCLUSION:The metastasis suppressor gene KAI1 might take part in influencing the lung metastasis of osteosarcoma,which might be caused by inhibiting the tumor cell proliferation,adhesion and invasion.     

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.