野黄芩苷联合奥沙利铂对结肠癌细胞的作用  

Effects of the combination therapy of scutellarin and oxaliplatin on colon cancer cells

作　　者：杨海军 严宝飞 张宁 刘美辉 YANG Hai-jun;YAN Bao-fei;ZHANG Ning;LIU Mei-hui(Jiangsu Health Vocational College,Nanjing 211800,China)

机构地区：[1]江苏卫生健康职业学院,江苏南京211800

出　　处：《中成药》2022年第10期3157-3163,共7页Chinese Traditional Patent Medicine

基　　金：江苏省科技成果转化专项项目(BA2018002);南京市浦口区科技局社会事业项目(S2017-6);江苏卫生健康职业学院校级课题重点项目(JKB202003)。

摘　　要：目的 探讨野黄芩苷联合奥沙利铂对结肠癌HCT116细胞活力、凋亡和自噬的作用及可能机制。方法 在体外将HCT116细胞分为空白组、野黄芩苷组、奥沙利铂组、野黄芩苷+奥沙利铂组,并给予相应药物处理。采用CCK8法检测HCT116细胞活力,Hochest染色和流式细胞术(Annexin V/PI双染)检测细胞凋亡情况,JC-1线粒体膜电位试剂盒检测细胞线粒体膜电位,Western blot法检测细胞凋亡、自噬及上游相关蛋白表达。结果 野黄芩苷、奥沙利铂均呈剂量依赖性地抑制HCT116细胞活力,24 h IC_(50)值分别为185.10、40.05μmol/L。与单用奥沙利铂组比较,野黄芩苷能协同奥沙利铂抑制HCT116细胞活力(P<0.05),促进细胞凋亡(P<0.01),升高cleaved caspase-3、p53蛋白表达,ERK1/2蛋白磷酸化水平及LC3-Ⅱ/LC3-Ⅰ、Bax/Bcl-2蛋白表达比值(P<0.01),降低细胞线粒体膜电位,p62、c-Met蛋白表达及Akt蛋白磷酸化水平(P<0.01)。结论 野黄芩苷能够协同奥沙利铂抑制HCT116细胞活力,并诱导凋亡和自噬,其潜在机制可能与激活ERK/p53信号通路和抑制c-Met/Akt信号通路有关。AIM To investigate the effects and possible mechanism of scutellarin combined with oxaliplatin on the viability, apoptosis and autophagy of colon cancer HCT116 cells.METHODS HCT116 cells were divided into the blank group, scutellarin group, oxaliplatin group and the combination therapy group(both scutellarin and oxaliplatin use) for corresponding drug treatment in vitro. HCT116 cells had their viability detected by CCK8 method;their apoptosis detected by Hochest staining and flow cytometry(Annexin V/PI double staining);their mitochondrial membrane potential detected by JC-1 mitochondrial membrane potential kit;and their expressions of apoptosis, autophagy and upstream related proteins detected by Western blot.RESULTS Both being dose-dependent HCT116 cells viability inhibitor, scutellarin and oxaliplatin presented 185.10 and 40.05 μmol/L IC_(50)values at 24 h, respectively. Compared with the single use of oxaliplatin, the combinative use of scutellarin and oxaliplatin upon HCT116 cells synergistically inhibited their viability(P<0.05), promoted their apoptosis(P<0.01), increased their expressions of cleaved caspase-3 and p53 proteins, ERK1/2 protein phosphorylation level and the ratios of LC3-Ⅱ/LC3-Ⅰ and Bax/Bcl-2 protein expressions(P<0.01), and reduced their mitochondrial membrane potential, p62 and c-Met protein expressions, and Akt protein phosphorylation level as well(P<0.01).CONCLUSION Upon HCT116 cells, the combination treatment of scutellarin and oxaliplatin can synergistically inhibit their viability, induce their apoptosis and autophagy, whose potential mechanisms may be related to the activation of ERK/p53 signaling pathway and the inhibition of c-Met/Akt signaling pathway.

关 键 词：野黄芩苷 奥沙利铂 结肠癌 协同增效 ERK/p53信号通路 c-Met/Akt信号通路 

分 类 号：R285.5[医药卫生—中药学]