缺血再灌注对肝癌细胞多重耐药表型的影响  

Effect of ischemia reperfusion on multi-drug resistance phenotype of hepatocellular carcinoma cells

作　　者：陈文军[1] 王庆大[2] 彭方毅[2] 崔萧 赵军[2] 贺凯[2] 苏松[2] 李波[2] 

机构地区：[1]泸州医学院附属中医医院肛肠科,四川泸州646000 [2]泸州医学院附属医院肝胆外科,四川泸州646000 [3]四川宜宾市第二人民医院肝胆外科,四川宜宾644000

出　　处：《中国现代医学杂志》2015年第22期22-27,共6页China Journal of Modern Medicine

基　　金：四川省杰出青年学术带头人培育计划(No:2011JQ0033);泸州市-泸州医学院联合基金项目(No:2013LZLY-J19)

摘　　要：目的通过检测人肝癌细胞株Hep G2细胞与人肝癌耐药细胞株Hep G2/ADM细胞缺血再灌注后多药耐药基因1(MDR1)、多药耐药相关蛋白2(MRP2)、P-gp和LRP表达及细胞增殖变化,探讨缺血再灌注与肝癌细胞多重耐药表型间的关系。方法用灌注液与缺血液分别灌注Hep G2、Hep G2/ADM细胞,RT-PCR检测每组细胞MDR1和MRP2表达水平,Western blot检测P-gp和LRP表达水平,MTT检测细胞阿霉素(ADM)、5-氟尿嘧啶(5-FU)对肝癌细胞的生长抑制率。结果缺血再灌注组Hep G2细胞相对于灌注液持续灌注组Hep G2细胞MDR1、MRP2、P-gp和LRP的表达均明显增强,差异具有统计学意义(P<0.05),抗肿瘤药物对细胞增殖抑制率减弱。而缺血再灌注组Hep G2/ADM细胞相对于灌注液持续灌注组Hep G/ADM细胞MDR1、MRP2、P-gp和LRP表达及肿瘤药物对细胞增殖抑制率均无明显改变,差异无统计学意义(P>0.05)。结论缺血再灌注可以使Hep G2细胞多重耐药基因及蛋白表达增加,从而对抗肿瘤药物产生抵抗,参与多重耐药的形成。[Objective] To investigate the relationship between ischemia reperfusion and multi-drug resistance phenotype of hepatocellular carcinoma by detecting the expression of MDR1, P-gp, MRlY2, LRP and cellular prolif- eration inhibition rate after ischemia reperfusion in HepG2 cell line and HepG2/ADM cell line. [ Methods ] Both the two cell hnes were experienced continuous perfusion or ischemia reperfusion. RT-PCR was used to determine the expression of MDR1 and MRP2. The levels of P-gp, LRP were assessed by Western blot. The cellular proliferation inhibition rate induced by ADM, 5-Fu was analyzed by MTF. [ Results ] For HepG2 cell line, compared with con- tinuous perfusion group, the expression level of MDR1, MRP, P-gp, LRP was significantly increased in ischemia reperfusion group （P 〈 0.05）, the cellular proliferation inhibition rate was lower. But for HepG2/ADM cell line, there was no difference between continuous perfusion group and ischemia reperfusion group （P 〉 0.05）. [ Conclusions ] Is- chemia reperfusion could increase the expression level of MDR genes, MDR proteins and lead to resistance to anti- neoplastic drugs in HepG2 cell line, and it is involved in the foImation of multi-drug resistance.

关 键 词：肝癌细胞 缺血再灌注 多药耐药 

分 类 号：R363.21[医药卫生—病理学]