摘要
目的观察三氧化二砷(As2O3)对人乳腺癌MDA MB231细胞的生物学效应及其作用机制。方法采用MTT法观察细胞毒性;膜联蛋白V(AnnexinV)异硫氰酸荧光素(FITC)+碘化丙啶(PI)双参数检测细胞凋亡;流式细胞术测定细胞周期、增殖细胞核抗原(PCNA)、凋亡相关蛋白Fas和bcl2阳性细胞百分率及细胞内钙离子(IECa2+)含量变化。结果As2O3可显著抑制MDA MB231细胞生长,且剂量效应关系差异有统计学意义(r=0.99,P<0.01),其IC50为6.65μmol/L;MDA MB231细胞经As2O3处理后可观察到凋亡;As2O3能上调Fas蛋白表达和IECa2+含量(P<0.01),下调PCNA蛋白表达(P<0.01),并使细胞周期阻滞在S+G2/M期,但对bcl2表达无影响(P>0.05)。结论As2O3在体外可显著抑制MDA MB231细胞生长并引起凋亡,其机制可能与上调Fas表达和IECa2+含量、降低PCNA表达及阻滞细胞周期有关。
Objective The study was to research the biological effect and mechanisms of arsenic trioxide(As_2O_3) on human breast cancer cell line MDA-MB-231. Methods The cytotoxicity was observed by MTT assay. Apoptosis was detected with Annexin V-FITC+PI dual parameter. Cell cycle and positive rate of proliferation cell nuclear antigen (PCNA), apoptosis associated protein Fas and bcl-2 and intracellular calcium ions(IECa^2+ ) levels were measured by flow cytometry. Results As_2O_3 could inhibit the growth of MDA-MB-231 cells dramatically. There was obvious dosage-effect correlation (r=0.99, P<0.01), its half inhibitory concentration(IC_~50 ) was 6.65 μmol/L. Apoptosis was observed in MDA-MB-231 cells treated with As_2O_3. As_2O_3 could increase Fas expression and IECa^2+ levels and decrease PCNA expression in MDA-MB-231 cells (P<0.01). Cell cycle was arrested in S+G_2/M phase , but bcl-2 protein expression were not affected(P>0.05). Conclusion As_2O_3 could inhibit the growth of MDA-MB-231 cells dramatically and induce apoptosis .We proposed that its mechanisms were probably associated with the improved Fas expression and IECa^2+ levels and decreased PCNA expression and cell cycle arrest.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第17期1209-1213,共5页
National Medical Journal of China
