摘要
目的:对一种热休克蛋白90抑制剂即17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG)对人乳腺癌细胞生长的影响及相关机制进行初步探讨。方法:MTT法检测药物对人乳腺癌细胞SKB r3的生长抑制作用;流式细胞术分析细胞凋亡及细胞周期变化;免疫组化法检测药物处理前后SKB r3细胞中HER2的表达变化情况。结果:17-AAG对人乳腺癌细胞株SKB r3生长有抑制作用,随着用药浓度的增加,抑制作用明显增强,呈明显的剂量依赖性,其IC50浓度为3.09μg/m l。SKB r3细胞经17-AAG处理48 h后,流式细胞仪分析可见在0、0.625、1.250、2.500、5.000和10.000μg/m l浓度下,SKB r3细胞的凋亡率分别为(1.03±0.08)%、(3.68±0.67)%、(7.06±1.12)%、(11.23±1.36)%、(20.32±1.98)%和(31.65±2.96)%;G0/Gl期细胞分别为58.61%、54.34%、49.55%、43.73%、35.52%和27.46%;S期细胞分别为:29.57%、25.21%、19.65%、22.98%、19.71%和15.46%;G2/M期细胞分别为11.82%、20.45%、30.18%、33.29%、44.77%和57.08%;同时17-AAG处理后的SKB r3细胞人类表皮生长因子受体2(HER2)表达明显减少。结论:17-AAG能够抑制人乳腺癌细胞SKB r3的生长并促进其凋亡,提示17-AAG是一种很有前景的抗肿瘤药物。
Objective ： To study the anti-proliferation effects of a heat shock protein 90 （Hsp90） inhibitor, 17-allylamino-17-demethoxygeldanamycin （17-AAG）, on a human breast cancer cell line, SKBr3, and related mechanism. Methods：MTT assay was used to detect the growth inhibition of SKBr3 cells. Cell cycle and apoptosis were analyzed by flow cytometry. Alteration of human epidermal growth factor receptor 2 （HER2） in SKBr3 cells being treated with 17-AAG were measured by immunohistochemistry. Results ： 17-AAG significantly inhibited growth of SKBr3 cells in vitro in a dose-dependent manner with an IC50 value at 3.09 μg/ml. Under concentrations of 0, 0. 625, 1. 250, 2. 500, 5. 000 and 10. 000 μg/ml,the percentages of cell apoptosis were （1.03 ±0.08）%, （3.68 ±0.67）%, （7.06 ±1.12）%,（ 11.23 ± 1.36 ） %, （20. 32 ± 1.98 ） %, and （ 31.65 ± 2.96 ） % ; the percentages of cells at G0/G1 phase were 58.61% , 54.34% , 49.55% , 43.73% , 35.52% , and 27.46% ;the percentages of cells at S phase were 29.57%, 25.21% , 19.65% , 22.98%, 19.71% , and 15.46% ;the percentages of cells at G2/M phase were 11.82%, 20.45%, 30.18%, 33.29%, 44.77%, and 57.08%, respectively. The level of HER2 expression in SKBr3 ceils being treated with 17-AAG, compared to that in control cells, was reduced significantly. Conclusion ： 17-AAG can inhibit the growth of human breast cancer cell and enhance its apoptosis. It may be a promising anti-tumor drug.
出处
《医学研究生学报》
CAS
2006年第12期1059-1062,I0017,共5页
Journal of Medical Postgraduates
基金
国家自然科学基金资助项目(批准号:30470500)
