蛋白酶体抑制剂硼替佐米联合顺铂对宫颈癌细胞增殖的影响  

Effects of proteasome inhibitor bortezomib combined with cisplatin on proliferation of human cervical cancer cells

作　　者：丁长宽 陈健行[1] 

机构地区：[1]山东大学癌症研究中心,山东济南250012

出　　处：《山东大学学报（医学版）》2018年第1期70-75,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81471944)

摘　　要：目的观察蛋白酶体抑制剂硼替佐米(BTZ)联合顺铂(CIS)对宫颈癌He La细胞增殖的影响并研究其相关机制。方法将Hela细胞分为NC组、CIS组、BTZ组、C&B组,分别以DMEM培养液、含CIS的培养液、含BTZ的培养液、含CIS及BTZ的培养液培养。以CCK-8法检测各组细胞的增殖抑制率,Western blotting法检测各组细胞中p53与Rb蛋白的表达水平,流式细胞仪检测细胞凋亡率。组间比较采用析因设计资料的方差分析。结果C&B组细胞增殖抑制率高于其他各组(P<0.05)。CIS组及C&B组中p53表达量较高(P<0.05),BTZ组与NC组相比差异无统计学意义。与NC组相比,BTZ组Rb表达量较高(P<0.05),CIS组、C&B组与NC组相比,差异无统计学意义。流式结果示CIS和BTZ在诱导细胞凋亡方面具有交互作用。结论 CIS可能通过调控p53通路对宫颈癌He La细胞增殖产生抑制作用,而BTZ可能通过调控Rb通路对宫颈癌He La细胞增殖产生抑制作用,且BTZ与CIS联用在抑制He La细胞增殖方面具有协同交互作用。Objective To investigate the effects of proteasome inhibitor bortezomib （ BTZ）, cisplatin （CIS） and their combination on proliferation of cervical cancer cells and to explore the mechanisms involved. Methods Hela cells were divided into four groups： normal control group （ NC group）, BTZ group, CIS group and C＆B group. Cell Counting Kit-8 （CCK-8） was used to examine HeLa cell proliferation after treatment. Western blotting was used to investigate the expression of p53 protein and Rb protein in the treated cells. Flow cytometry was used to observe apoptosis ratio after treatment. Results The inhibitory effect on the proliferation of HeLa cells in the C＆B group was higher compared with the other groups. Western blotting analysis showed that the expression of p53 protein in CIS group was higher than that in NC group and C＆B group（P〈0.05）, but had no obvious difference in BTZ group. Compared with that in other three groups, the expression of Rb protein in BTZ group was higher（ P〈0.05）, and no obvious change was observed among these three groups. Flow cytometry demonstrated a synergistic effect of BTZ and CIS on HeLa cell apoptosis. Conclusion CIS may inhibit the proliferation of HeLa cells via regulating the expression of p53 ; BTZ may inhibit the proliferation of HeLa cells via regulating the expression of Rb ; BTZ could enhance the inhibitory effects of CIS on HeLa cells.

关 键 词：蛋白酶体抑制剂 硼替佐米 顺铂 p53蛋白 RB蛋白 HELA细胞 宫颈癌 

分 类 号：R741.05[医药卫生—神经病学与精神病学]