蛋白酶体抑制剂硼替佐米抑制PI3K/Akt通路致结肠癌SW480细胞凋亡  

Proteasome Inhibitor Brotezomib Induces Apoptosis of Colon Cancer Cells SW480 through Inhibiting PI3K/Akt Pathway

作　　者：王鹤霏[1] 封斌[1] 孙艺[1] 唐光波[1] 闵捷[2] 王新[1] 

机构地区：[1]第四军医大学西京消化病医院肿瘤生物学国家重点实验室,陕西西安710032 [2]第四军医大学西京医院全军眼科研究所,陕西西安710032

出　　处：《现代生物医学进展》2013年第11期2044-2048,共5页Progress in Modern Biomedicine

基　　金：国家重点基础发展计划项目973计划(2009CB521705)

摘　　要：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。Objective： In the basis of the human colon cancer SW480 cells treated with bortezomib could induce cell apoptosis,then we aim to explore the possible mechanism involved.Method： Human colon cancer SW480 cells were routinely cultured in vitro and treated with different concentrations of bortezomib（1-500 nmol/L） for 24-48 h.The changes of cell growth and apoptosis were investigated by MTT assay and Annexin-V/PI double dyeing assay.The protein levels of cleavage of caspase-3,phosphor-Akt and PTEN were determined by Westen bolt.Results： Bortezomib significantly inhibited the proliferation of SW480 cells in a dose-and time-dependent manner.The IC50 value at 48 h was 87.36 nmol/L.Cells treated with both 40 and 160 nmol/L of bortezomib induced apoptosis at 24 h and obviously induced apoptosis at 48 h.At 24 h,treated with bortezomib,SW480 cell showed a cycle arrest at G0/G1 phase.The protein level of PTEN was obviously up-regulated while phosphor-Akt level was down-regulated in SW480 cells treated with 80 nmol/L of bortezomib at 48 h by Western Blot.Conclusion： We propose that by suppressing the degradation of PTEN,the bortezomib could effectively affect the PI3K/Akt signaling path way in human colon cancer SW480 cells.

关 键 词：硼替佐米 结肠癌 细胞凋亡 PI3K AKT 

分 类 号：Q78[生物学—分子生物学]