摘要
目的:观察硼替佐米对胃癌细胞的抗肿瘤作用,并探讨其相关的作用机制。方法:MTT生长抑制实验检测硼替佐米对胃癌SGC-7901细胞的细胞毒作用;PI和AnnexinV-FITC双染流式细胞仪检测细胞凋亡情况;Westernblot实验检测蛋白的表达变化。结果:硼替佐米对胃癌SGC-7901细胞的IC50值为(54.6±4.1)nmol/L。0、50、100nmol/L硼替佐米作用于SGC-7901细胞48h后,细胞的凋亡率分别为(1.8±0.7)%、(26.5±4.6)%、(41.7±5.8)%,各组之间具有统计学差异(P<0.01)。50和100nmol/L的硼替佐米作用SGC-7901细胞48h后,细胞出现了Parp和caspase-3蛋白的裂解带。50和100nmol/L的硼替佐米作用SGC-7901细胞48h后,细胞Bmi-1蛋白的表达出现了显著的降低。结论:硼替佐米对胃癌SGC-7901细胞具有显著的抗肿瘤活性,下调Bmi-1蛋白可能是其诱导胃癌细胞凋亡的主要作用机制。
ABSTRACT OBJECTIVE： To study the cytotoxic activity of bortezomib against gastric cancer and its action mechanism. METHODS： MTT assay was used to detect the cytotoxic activity of bortezomib against gastric cancer SGC-7901 cells. The apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry analysis. The protein expression was determined by western blot analysis. RESULTS： The IC50 values of bortezomib against SGC-7901 cells was 54.6± 4.12 nmol/L. After treatment with 0, 50, and 100 nmol/L bortezomib for 48 h, the percent of apoptosis was elevated from 1.8±0.7 to 26.5±4.6 and 41.7±5.8% , respectively. There was significant difference among the different treatment（P〈0.01）. After treatment with 50 and 100 nmol/L bortezomib for 48 h, the cleaved-Parp and cleaved-caspase-3 was detected by Western blot analysis. After treatment with 50 and 100 nmol/L bortezomib for 48 h, the protein expression of Bmi-1 was downregulated. CONCLUSION： Bortezomib showed significant anticancer activity against gastric cancer SGC-7901 cells. The downregulation of Bmi-1 protein to induce apoptotic pathway may played an important role in its action mechanism.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2013年第6期606-609,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
