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目的:研究蛋白酶体抑制剂硼替佐米对结肠癌SW480细胞凋亡作用,并进一步探讨其作用机制。方法:硼替佐米1-500nmol/L处理结肠癌SW480细胞24-48小时,MTT法检测细胞存活率、药物IC50值。流式细胞术检测细胞凋亡率。Westernblot技术检测caspase-3,p-Akt和PTEN蛋白表达水平变化。结果:硼替佐米以时间-剂量依赖方式抑制结肠癌SW480细胞增殖,48小时IC50值:87.36 nmol/L。细胞凋亡实验显示药物作用24小时细胞开始出现凋亡,48小时凋亡明显。硼替佐米作用24小时后细胞周期明显阻滞在G0/G1期。Western blot实验显示,80 nmol/L硼替佐米处理结肠癌SW480细胞后PTEN蛋白表达水平随时间明显增加,而p-Akt蛋白随时间表达下降。结论:硼替佐米可以抑制结肠癌SW480细胞增殖。其机制可能与抑制PTEN蛋白降解,抑制p-Akt途径有关。为结肠癌治疗药物的发展和更新提供了新的候选分子。
AIM: To investigate the apoptosis effect of proteasome inhibitor bortezomib on human colon cancer SW480 cells and to explore its mechanism. Methods: Colon cancer SW480 cells were treated with bortezomib at 1-500 nmol / L for 24-48 hours. Cell viability and drug IC50 values were determined by MTT assay. Flow cytometry was used to detect the apoptosis rate. Westernblot technique was used to detect the expression of caspase-3, p-Akt and PTEN. RESULTS: Bortezomib inhibited the proliferation of colon cancer SW480 cells in a time-and dose-dependent manner with an IC50 value of 87.36 nmol / L at 48 hours. Apoptosis experiments showed that the cells began to show apoptosis 24 hours after drug treatment, and the apoptosis was obvious at 48 hours. Bortezomib 24 hours after cell cycle arrest in the G0 / G1 phase. Western blot showed that the expression of PTEN protein in the colon cancer SW480 cells treated with 80 nmol / L bortezomib increased significantly with time, while p-Akt protein decreased with time. Conclusion: Bortezomib can inhibit the proliferation of colon cancer SW480 cells. The mechanism may be related to the inhibition of PTEN protein degradation, inhibition of p-Akt pathway. It provides new candidates for the development and renewal of colon cancer drugs.