Selenium dioxide induces leukemia cell apoptosis and changes of intracellular reactive oxygen species (ROS) and Ca2+ levels

AIM: The effects of selenium dioxide (SeO2) on proliferation, apoptosis, intracellular reactive oxygen species (ROS) and Ca2+ levels in three leukemia cell lines NB4, K562 and HL-60 were investigated. METHODS: Three leukemia cell lines were treated with 3-30 μmol/L SeO2. Flow cytometry was used to detect apoptosis rate, and analyze the changes of ROS and Ca2+ level within cells. RESULTS: SeO2 at 10 and 30 μmol/L inhibited proliferation in three leukemia cell lines. Treatment with 30 μmol/L SeO2 for 48 h induced 54.0%, 46.5%, 49.6% apoptosis in NB4, K562, and HL-60 cells, respectively, and also markedly decreased ROS and Ca2+ levels among three cell lines. The rate of ROS positive cells in NB4 and HL-60 decreased with the increase in SeO2 concentrations. ROS was clearly reduced with 30 μmol/L SeO2 in K562. Ca2+ levels were tardily declined with 10, 30 μmol/L SeO2 in NB4 and HL-60 cells. Ca2+ levels were clearly reduced with 30 μmol/L SeO2 in K562. CONCLUSION: SeO2 induces apoptosis in three leukemia cells. The declines of intracellular ROS and Ca2+ levels are involved in apoptosis induced by SeO2.     

Effect of lentinan on apoptosis and PI3K/AKT signaling pathway in leukemic HL-60 cells in vitro

AIM:To study of the regulatory effect of lentinan on human leukemic HL-60 cell apoptosis and its effect on PI3K/AKT signaling pathway in HL-60 cells in vitro.METHODS:Lentinan at concentrations of 0 mg/L, 15 mg/L, 30 mg/L and 45 mg/L was applied to HL-60 cells cultured to the logarithmic phase in vitro, and the inhibitory effect of lentinan on the viability of HL-60 cells was measured by MTT assay after 24 h, 48 h and 72 h. The apoptosis induced by lentinan was analyzed by flow cytometry. The protein levels of cleaved PARP, cleaved caspase-9, cleaved caspase-3, cleaved caspase-8, cytochrome C, PI3K, AKT and p-AKT were determined by Western blot. After treatment with PI3K inhibitor LY294002 at 5 mg/L for 72 h, the apoptosis of HL-60 cells was analyzed by flow cytometry. RESULTS:The viability of HL-60 cells was inhibited after treatment with lentinan at concentrations of 15 mg/L, 30 mg/L and 45 mg/L for 24 h, 48 h and 72 h in concentration-dependent and time-dependent manners (P<0.05). The apoptosis of HL-60 cells was promoted after treatment with lentinan (15 mg/L, 30 mg/L and 45 mg/L) for 72 h in a concentration-dependent manner (P<0.05). The protein levels of cleaved PARP, cleaved caspase-9, cleaved caspase-3 and cytoplasmic cytochrome C in the HL-60 cells induced by 30 mg/L lentinan were increased significantly with the increase in the treatment time (P<0.05), but caspase-8 did not show any change. The protein levels of PI3K, AKT and p-AKT were decreased obviously with the increase in the lentinan concentration (P<0.05). Treatment of HL-60 cells with LY294002, a PI3K pathway inhibitor, produced apoptosis-inducing effect similar to lentinan (P<0.05). CONCLUSION:Lentinan induces HL-60 cell apoptosis by inhibiting PI3K/AKT signaling pathway.     

Knockdown of RALA by siRNA inhibits cell proliferation and induces apoptosis in human leukemic K562 cells

AIM: To investigate the effect of siRNA-induced knockdown of v-ral simian leukemia viral oncogene homolog A(RALA) on proliferation and apoptosis of chronic myelogenous leukemia(CML) K562 cells. METHODS: The chemically synthesized siRNA targeting to RALA gene was transfected into K562 cells using Lipofectamine^TM 2000. The proliferation and viability of K562 cells were detected by MTT assay and trypan blue dye exclusion. The expression levels of RALA mRNA and protein were determined by quantitative real-time PCR and Western blotting,respectively. The cell apoptosis was analyzed using flow cytometry by double staining with annexin V and propidium iodide, and the apoptotic morphological changes were detected by Hoechst 33258 staining. RESULTS: RALA siRNA significantly down-regulated RALA mRNA and protein expression in K562 cells(P<0.05). The proliferation of K562 cells in RALA siRNA group was inhibited compared with control group(P<0.05). The apoptotic rate was much higher in RALA siRNA group than that in negative control group(P<0.05). The apoptotic morphological changes were observed in the nuclei of K562 cells transfected with RALA siRNA. CONCLUSION: The siRNA-mediated knockdown of RALA results in inhibition of proliferation and induction of apoptosis in K562 cells, indicating that RALA might be used as a potential therapeutic target in chronic myelogenous leukemia.     

Reversal of apoptosis resistance of doxorubicin-resistant human myelogenous leukemia cell line K562/DOX by a cyclosporin D analogue PSC833

AIM:To study the reversal effect of a cyclosporin D analogue PSC833 on multidrug resistance of doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. METHODS:The reversal effects of PSC833 on resistance to doxorubicin (DOX)/vincristine (VCR) in K562/DOX cells were observed by MTT assay. The cell cycle analysis was performed by flow cytometry. Annexin V/PI staining was used to identify PSC833-induced apoptosis in K562/ DOX cells. These cells underwent incubation with DCFH-DA, JC-1 and Fluo-3/AM followed by flow cytometry for the measurement of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and intracellular calcium, respectively. The protein levels of cytochrome C (Cyt C), Bcl-2, Bax, and cleaved caspase-3 were detected by Western blotting. RESULTS:The DOX/VCR-induced cytotoxicity was significantly potentiated by PSC833. PSC833 arrested the cells in G2/M phase and increased the apoptosis induced by DOX in K562/DOX cells. During the apoptosis, the level of ROS and intracellular calcium increased, while the level of ΔΨm decreased. Furthermore, the release of Cyt C, activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2 were observed in K562/DOX cells treated with PSC833 and DOX. CONCLUSION: The reversal effect of PSC833 on multidrug resistance in K562/DOX cells is associated with the induction of apoptosis through a mitochondria-dependent pathway.     

Celecoxib inhibits viability,induces apoptosis and inhibits autophagy in acute myeloid leukemia cell lines HL-60 and HL-60A

AIM: To investigate the effects of celecoxib on viability, apoptosis and autophagy in acute myeloid leukemia (AML) cell lines HL-60 and HL-60A. METHODS: The HL-60 cells and HL-60A cells were cultured with various concentrations (0, 20, 40, 60, 80 and 100 μmol/L) of celecoxib. The inhibitory effect of celecoxib on the cell viability was evaluated by MTT assay. Apoptosis was analyzed by Annexin-V/PI staining. Apoptosis-related and autophagy-related proteins were determined by Western blot. RESULTS: IC₅₀ of celecoxib were 49.4 μmol/L, 32.0 μmol/L and 25.1 μmol/L for HL-60 cells treated with celecoxib for 24 h, 48 h and 72 h, respectively. For HL-60A cells, the corresponding IC₅₀ were 69.1 μmol/L, 42.5 μmol/L and 29.6 μmol/L, respectively. The results of flow cytometry analysis showed the proportions of Annexin-Ⅴ⁺ PI^-, Annexin-Ⅴ⁺ PI⁺ and Annexin-Ⅴ^-PI⁺ cells were increased in the HL-60 cells, and those of Annexin-Ⅴ⁺PI^- and Annexin-Ⅴ⁺ PI⁺ cells were increased in the HL-60A cells treated with celecoxib for 24 h. After treated with celecoxib, the induction of apoptosis was observed, the apoptosis-related proteins cleaved caspase-3 and cleaved PARP were upregulated, the autophagy-related proteins LC3 II and P62 were both increased, and mTOR, p-mTOR, 4-EBP and p-4-EBP were not changed, indicating that celecoxib inhibited autophagy in the AML cells without the mTOR pathway involvement. CONCLUSION: Celecoxib inhibits the viability of HL-60 cells and HL-60A cells in a time-and dose-dependent manner by its effects of inducing apoptosis and necrosis. Celecoxib inhibits mTOR-independent autophagy in AML cells, indicating a possible way of using celecoxib for enhancing the antitumor activity of therapeutic agents to induce cytoprotective autophagy in the AML cells.     

Sodium aescinate induces apoptosis of HeLa cells by inhibiting Akt/ERK signaling pathways and increasing death receptor expression

AIM:To study the effects of sodium aescinate on the apoptosis of cervical cancer HeLa cells and its molecular mechanism. METHODS:MTT assay was used to detect the growth and proliferation of HeLa cells. The morphological alteration was observed under inverted microscope. Annexin V-FITC/PI double staining and DAPI nuclear staining were used to determine the apoptosis of HeLa cells induced by sodium aescinate. The apoptosis-related proteins PARP, cleaved caspase-8 and pro-caspase-3, and the proliferation-associated molecules Akt and ERK, as well as TRAIL receptors DR4 and DR5 were detected by Western blotting. RESULTS:Sodium aescinate inhibited the growth of HeLa cells in a concentration-dependent manner. Treatment with sodium aescinate induced the typical morphology of apoptotic cells and increased the apoptotic rate significantly. The cleaved PARP, cleaved caspase-8 and cleaved caspase-9 protein expression was observed. The expression of DR4 and DR5 was up-regulated. Meanwhile, pro-caspase-3 was decreased, and the levels of p-Akt and p-ERK were down-regulated by sodium aescinate in a dose-dependent manner. CONCLUSION:Sodium aescinate inhibits the proliferation and promotes the apoptosis of HeLa cells by increasing death receptor expression and repressing proliferation-associated signaling pathways.     

Transition of WT1 isoforms inhibits proliferation and promotes apoptosis of human leukemia cell line HL-60

AIM: To study the potential effects of exogenous Wilms tumor 1 (WT1) isoforms on the proliferation and apoptosis of human leukemia cell line HL-60. METHODS: WT1 (17AA－/KTS－) gene obtained by RT-PCR was cloned into a PCDH1-MCS1-EF1-copGFP plasmid. The recombinant plasmid was confirmed by enzyme digestion and sequencing, and was transfected into HL-60 cells by LipofectamineTM 2000. The stable transformants were selected by G418 screening. WT1(17AA－/KTS－) expression was identified by real-time fluorescence quantitative RT-PCR and Western blotting. The proliferation of the cells was measured by MTT assay. The apoptosis of the cells was determined by morphological observation and flow cytometry analysis. RESULTS: The eukaryotic expression vector PCDH1-MCS1-EF1-copGFP-WT1 (17AA－/KTS－) was successfully constructed. The recombinant cells exhibited high mRNA and protein levels of WT1(17AA－/KTS－). The growth of recombinant cells was slower than that of HL-60 cells transfected with control vector and normal HL-60 cells. After exposed to As2O3 at 2 μmol/L for 48 h, both recombinant cells and control cells exhibited the morphological characteristics of apoptosis, but the former was more typical than the latter. The apoptosis was enhanced in the recombinant cells after the cells were exposed to As2O3 for 24 h. CONCLUSION: Exogenous WT1(17AA-/KTS-) isoform inhibits the proliferation and promotes the apoptosis of leukemic cells.     

FoxM1 promotes development of AML by regulating Bcl-2 expression

AIM: To investigate the role of Forkhead box M1 (FoxM1) and B-cell leukemia/lymphoma-2 (Bcl-2) in the pathogenesis of acute myeloid leukemia (AML). METHODS: RT-qPCR and immunofluorescence analysis were used to determine the expression of FoxM1 at mRNA and protein levels in AML-de novo patients, AML-complete remission (CR) patients, AML-refractoriness and relapse (RR) patients and healthy controls. HL60 cells and K562 cells were transfected with FoxM1 siRNA. The cell proliferation was detected by cell proliferation assay and colony formation assay on soft agar, and the cell apoptosis was determined by flow cytometry. The expression of FoxM1 and Bcl-2 at mRNA and protein levels was detected by RT-qPCR and Western blotting. The activity of bcl-2 promoter was examined by luciferase reporter assay with FoxM1 targetting. RESULTS: FoxM1 expression level in the AML-de novo patients was significantly higher than that in the healthy controls. As compared with the AML-de novo patients, FoxM1 expression in the AML-CR patients was reduced, and the FoxM1 expression level was the highest in the AML-RR patients. FoxM1 expression was inhibited in the HL60 cells and K562 cells transfected with FoxM1 siRNA. Transfection with FoxM1 siRNA in the HL60 cells and K562 cells inhibited the proliferation as compared with NC siRNA transfection, and impaired the colony formation ability. On the contrary, transfection with FoxM1 siRNA promoted the cell apoptosis. FoxM1 regulated bcl-2 expression positively. CONCLUSION: FoxM1 promotes the development of AML by regulating bcl-2 expression. Silencing of FoxM1 expression suppresses cell proliferation and promotes cell apoptosis. FoxM1 is a potential target for AML treatment.     

Salinomycin inhibits proliferation and induces apoptosis of Gleevec-resistant chronic myeloid leukemic cell line K562/Glv

AIM: To study the effect of salinomycin on inhibiting proliferation and inducing apoptosis of Gleevec-resistant chronic myeloid leukemia cell line K562/Glv. METHODS: The inhibitory effect of salinomycin on the growth of K562/Glv cells was detected by CCK-8 assay in vitro. Flow cytometry was used to observe apoptosis, mitochondria membrane potential (ΔΨ_m), reactive oxygen species (ROS) and the concentration of intracellular Ca²⁺ ([Ca²⁺]_i) in K562/Glv cells. The activity of caspase-3, -8 and -9 was measured by the method of colorimetry. The levels of cytochrome C, Bcl-2, Bax, β-catenin and phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) were determined by Western blotting. RESULTS: Salinomycin inhibited the growth of K562/Glv cells in a dose-dependent manner. Salinomycin at concentration of 0.2 μmol/L inhibited the growth of the cells with the inhibitory rate of (36.70±2.31)%. The cell apoptotic rate was (19.66±2.23)%. Salinomycin at concentration of 0.2 μmol/L decreased the level of ΔΨ_m, and increased the levels of ROS, cytochrome C and[Ca²⁺]_i in the cells. Salinomycin also increased the activity of caspase-3, -8 and -9 in the cells, reduced the ratio of Bcl-2/Bax, and attenuated the levels of β-catenin and p-LRP6. CONCLUSION: Salinomycin induces the apoptosis of Gleevec-resistant myeloid leukemia cell line K562/Glv via Bcl-2/Bax and mitochondria-dependent pathways, and inhibits the cell growth through Wnt signal pathway.     

Effect of NF-κB inhibitor pyrrolidine dithiocarbonate on the proliferation and apoptosis in K562 cells

AIM: To investigate the effect of pyrrolidine dithiocarbamate (PDTC), a specific inhibitor of NF-κB on the proliferation and apoptosis of K562 cells and to explore the anti-tumor mechanism of PDTC.METHODS: Trans AMTM NF-κB p65 kit was used to detect the activity of p65 in K562 cells treated by PDTC. The effect of PDTC on the proliferation of K562 cells was measured by WST-1 method. DNA damage was detected by single cell gel electrophoresis (comet assay). The procaspase-3 and activated protein level of caspase-3 were detected by Western blotting.RESULTS: The activity of p65 in K562 cells was inhibited after treated by PDTC (P<0.01). Simultaneously the cell proliferation was significantly inhibited in a dose-and time-dependent manner (P<0.01). The degree of DNA damage in K562 cells treated with PDTC at concentrations of 25 μmol/L, 50 μmol/L or 100 μmol/L was more severe than that in control. The rates of comet cells in the PDTC-treated groups (43.50％, 84.00％, 95.63％) were significantly higher than those in control (9.75％, P<0.01), and it was also dose-dependent. The expression of procaspase-3 and activated caspase-3 protein were detected in the cytoplasm of the K562 cells treated by PDTC by Western blotting.CONCLUSION: NF-κB plays an important role in regulating cell proliferation and apoptosis in K562 cells. PDTC inhibits NF-κB activity and elevates the expression of caspase-3, which is related to increase in cell apoptosis.     

Effect of p19ARF on growth and apoptosis of leukemia cells

AIM:To study the effect of p19ARF on the biological behavior of human leukemia cells. METHODS:p19ARF was cloned in eukaryotic expression vector pcDNA3.1 and transferred into INK4a/ARF locus-deficient leukemia cells HEL and K562. The changes in biological characteristics of the two p19ARF-transfected cells were observed.RESULTS:The growth of the p19ARF-transfected HEL cells was significantly inhibited compared with the vector-transfected cells; Cell cycle analysis showed that the expression of foreign p19ARF gene resulted in G1 phase cell cycle arrest and apoptosis cell death in some of HEL cells. However, p19ARF had no marked effects on the growth of K562 cells with p53 gene mutation and did not induce apoptosis in K562 cells.CONCLUSION:p19ARF suppressed the growth of leukemia cells by p53-dependent pathway.     

Mechanism of 13-methyltetradecanoic acid in inducing bladder cancer T24 cell apoptosis in vitro

AIM: To study the effect of 13-methyltetradecanoic acid (13-MTD) on bladder cancer T24 cell apoptosis and the underlying mechanisms. METHODS: T24 cells were treated with 13-MTD at different concentrations. MTT cell proliferation assay was used to observe the inhibitory effect. The cell cycle and cell apoptosis were displayed by FCM. Apoptosis index was investigated by TUNEL assay. Western blotting was used to detect the expression of apoptosis related proteins. RESULTS: p38 and JNK phosphorylation were presented 2 h after stimulated by 13-MTD, but AKT phosphorylation were inhibited. Cytochrome C was released from the intermembrane space of mitochondria 8 h later. No change of FADD and p-FADD was observed. Several downstream caspase substrates (PARP, lamin B, RB) were cleaved in 12 h. CONCLUSION: In the course of T24 cell apoptosis induced by 13-MTD, JNK/SAPK and p38MAPK signaling pathway are activated and the PI3K/AKT signaling pathway is inhibited. The substrates of caspase: PARP, Rb, lamin B are cleavaged by activated caspase enzymes to promote T24 cell apoptosis.     

Antitumor mechanism of danusertib in human AML HL-60 cells

AIM: To investigate the effects of danusertib, a pan-inhibitor of Aurora kinases, on the viability, cell cycle, apoptosis and autophagy of human acute myelocytic leukemia (AML) HL-60 cells.METHODS: The effect of danusertib on the viability of HL-60 cells was examined by MTT assay. The effect of danusertib on apoptosis of HL-60 cells was quantitated by the flow cytometry using an Annexin V/7-AAD apoptosis detection kit. The effect of danusertib on autophagy in the HL-60 cells was assessed by flow cytometry and confocal microscopic analysis. The levels of various proteins related to the cell cycle, apoptosis and autophagy were determined by Western blot.RESULTS: Danusertib decreased the viability of human AML HL-60 cells and induced the cell cycle arrest in G₂/M phase. Danusertib also induced mitochon-drium-dependent apoptosis by activation of caspase-3 and autophagy in the HL-60 cells via inhibition of PI3K/Akt/mTOR signaling pathway.CONCLUSION: Danusertib shows effective antitumor ability for promising AML treatment.     

Effects of aspirin on apoptosis of homologous nasopharyngeal carcinoma cells with different radioresistance

AIM: To investigate the effects of aspirin on the apoptosis of nasopharyngeal carcinoma cell lines CNE2R and CNE2 with different radioresistance and its potential mechanism. METHODS: The effects of aspirin on the cell viability, apoptosis, and protein levels of procaspase-3, cleaved caspase-3, procaspase-9, procaspase-12, PARP and cleaved PARP, PI3K p110α, Akt, Bcl-2, Bax and p27 in the CNE2R cells and CNE2 cells were detected by the methods of MTT assay, flow cytometry and Western blot. RESULTS: Aspirin inhibited the viability of homologous nasopharyngeal carcinoma cell lines CNE2 and CNE2R (with the IC₅₀ to CNE2 cells of 6.18, 3.92 and 3.06 mmol/L for 24 h, 48 h and 72 h, respectively; and with the IC₅₀ to CNE2R cells of 7.05, 3.90 and 2.20 mmol/L for 24 h, 48 h and 72 h, respectively). After treated with aspirin for 48 h, the apoptotic rate of CNE2R cells was higher than that of CNE2 cells (P<0.05). After treated with aspirin for 48 h, the protein levels of procaspase-3, procaspase-9, procaspase-12 and PARP were decreased, the protein levels of cleaved caspase-3, cleaved PARP and p27 were increased, and the protein levels of PI3K p110α, Akt and Bcl-2/Bax were decreased. CONCLUSION: Aspirin inhibits the viability of homologous nasopharyngeal carcinoma cell lines CNE2R and CNE2 with different radioresistance. Aspirin also induces the apoptosis of CNE2 and CNE2R cells, which is more effective in CNE2R cells. The underlying mechanisms may be involved in affecting PI3K/Akt signaling pathway, Bcl-2/Bax and p27 expression.     

Inhibition of FoxM1 sensitizes leukemia K562 cells to homoharringtonine

AIM: To study whether inhibition of forkhead box protein M1(FoxM1) sensitizes leukemia K562 cells to homoharringtonine (HHT). METHODS: K562 cells were incubated with HHT at different concentrations (0μmol/L, 0.015μmol/L, 0.030μmol/L and 0.045μmol/L) for different time (0 h, 24 h, 48 h and 72 h). The mRNA and protein levels of FoxM1 were detected by real-time PCR and Western blot. FoxM1 siRNA was transfected into K562 cells with 0.015μmol/L HHT after 6 h. After 72 h incubation, the cell proliferation was detected by cell counting and soft agar assay, and the proportion of apoptotic K562 cells was determined by flow cytometry. The expression of c-Myc and Sp1 were detected by real-time PCR and Western blot. RESULTS: FoxM1 expression was reduced time-dependently and dose-dependently, suggesting that HHT mediated the downregulation of FoxM1 in K562 cells. In K562 cells, treatment with FoxM1 siRNA and HHT inhibited the cell proliferation and promoted the apoptosis significantly. Therefore, inhibition of FoxM1 sensitized leukemia K562 cells to HHT. The expression of c-Myc and Sp1 was positively regulated by FoxM1. CONCLUSION: HHT inhibits Forkhead box protein M1 expression in K562 cells. Inhibition of FoxM1 sensitizes K562 cells to HHT.     

Effect of gambogic acid on proliferation and apoptosis of human diffuse large B-cell lymphoma cell line OCI-LY-1

AIM: To investigate the effects of gambogic acid (GA) on the proliferation and apoptosis of human diffuse large B-cell lymphoma cells. METHODS: Diffuse large B-cell lymphoma cell line OCI-LY-19 was treated with GA. The cell viability and proliferation were evaluated by MTS assay. The morphological changes of the cells were observed under inverted microscope and fluorescence microscope with PI staining. The cell apoptosis was detected by flow cytometry. The changes of proteasome-related proteins Ubs, Bax, HSP90 and IκB-α, the apoptosis-related proteins PARP, pro-caspase-3 and caspase-8, and the proliferation-associated molecules ERK and STAT5 were detected by Western blotting. RESULTS: The proliferation of OCI-LY-19 cells was inhibited and the apoptosis was induced by GA. The expression of Ubs, Bax and HSP90 was up-regulated by GA treatment in a dose-dependent manner. The PARP protein was cleaved. The levels of apoptosis-related proteins pro-caspase-3 and pro-caspase-8, and proliferation-associated molecules p-Akt, p-ERK and p-STAT5 were down-regulated by GA treatment in a dose- and time-dependent manner. CONCLUSION: Gambogic acid down-regulates the activity of proteasome, inhibits cell proliferation and promotes cell apoptosis of diffuse large B cell lymphoma.     

Inhibition of c-Myc by 10058-F4 overcomes imatinib resistance in chronic myeloid leukemia cells

AIM：To investigate the effect of c-Myc inhibitor 10058-F4 on human chronic myeloid leukemia (CML) K562 cells and imatinib-resistant K562/G cells. METHODS：The protein expression of c-Myc was detected by Western blotting. Cell proliferation was evaluated by MTT assay and colony formation assay. PI staining was used to determine the cell cycle distribution. Annexin V-PI staining was applied for apoptosis detection. RESULTS：Imatinib-resistant K562/G cells displayed lower sensitivity to imatinib than K562 cells with high expression of c-Myc. Treatment with specific c-Myc inhibitor 10058-F4 inhibited the cell proliferation in a dose- and time-dependent manner, and K562/G displayed more sensitivity to 10058-F4 than K562 cells. 10058-F4 also induced cell cycle arrest in G0/G1 phase and induced apoptotic cell death in the 2 cells. Importantly, 10058-F4 suppressed the colony formation ability in K562 and K562/G cells. CONCLUSION：c-Myc is a novel target to overcome imatinib-induced drug resistance, and c-Myc inhibitor provides a new approach in CML therapy.     

姬松茸多糖抗肿瘤的实验研究

应用细胞培养技术 ,观察了姬松茸多糖对K5 6 2和HL - 6 0细胞系的影响。研究结果表明 ,实验组活细胞数、集落形成明显减少 ,荧光显微镜下所见凋亡细胞显著增加。提示姬松茸多糖具有抗肿瘤效果。为了探讨姬松茸多糖抗肿瘤的机理 ,本实验还应用反义寡聚脱氧核糖核酸技术 ,进一步观察了姬松茸多糖与人端粒酶反义核酸协同诱导HL - 6 0细胞系凋亡的作用 ,实验结果表明 ,姬松茸多糖与反义寡核苷酸联合使用 ,可促进HL- 6 0细胞凋亡。