益气化瘀解毒方对MRP、GST-π和Topo Ⅱ基因在Sorafenib获得性耐药人肝癌QGY7702细胞表达的干预研究  

Intervention Study of Yiqi Huayu Jiedu Prescription on the Expression of MRP, GST-π and Topo II Genes in Sorafenib Acquired Resistant Human Hepatocellular Carcinoma QGY7702 Cells

作　　者：王亚琪 曾普华[2,3] 郜文辉 李为[4] 张振[1] 周芳 俞淑娴[1] WANG Yaqi;ZENG Puhua;GAO Wenhui;LI Wei;ZHANG Zhen;ZHOU Fang;YU Shuxian(Hunan University of Chinese Medicine,Changsha 410208,China;Cancer Center,Affiliated Hospital of Hunan Academy of Chinese Medicine,Changsha 410006,China;Hunan Engineering Research Center for the Technology of Creation,Changsha 410006,China;The First Hospital of Hunan University of Chinese Medicine,Changsha 41020&China)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南省中医药研究院中医肿瘤研究所,长沙410006 [3]抗肿瘤中药创制技术湖南省工程研究中心,长沙410006 [4]湖南中医药大学第一附属医院,长沙410208

出　　处：《吉林中医药》2020年第4期505-509,共5页Jilin Journal of Chinese Medicine

基　　金：国家自然科学基金(81603603);湖南省科技计划项目(2016SK2051);湖南省中医药管理局重点课题(201803)。

摘　　要：目的探讨益气化瘀解毒方干预后对Sorafenib获得性耐药人肝癌QGY7702细胞(QGY7702/Sora)增殖及MRP、GST-π和Topo Ⅱ基因表达的影响。方法培养QGY7702/Sora细胞和QGY7702细胞,利用Cell Counting Kit-8(CCK-8)法检测Sorafenib对细胞的半数抑制率浓度(IC50值),计算耐药指数RI;观察益气化瘀解毒方对耐药细胞的增殖影响;采用荧光定量PCR检测药物干预前后2种细胞中MRP、GST-π和Topo Ⅱ基因表达水平。结果亲本细胞和耐药细胞Sorafenib的IC50值分别为(7.993±0.522)μmol/L和(19.651±1.216)μmol/L,RI约为2.5。益气化瘀解毒方可抑制耐药细胞的增殖活性。2种细胞的MRP、GST-π、Topo Ⅱ表达量无明显差异(P>0.05)。Sorafenib组可促进耐药细胞MRP 、GST-π基因的过表达(P<0.05),益气化瘀解毒方组可抑制GST-π基因的过表达(P<0.01),且联合Sorafenib可显著提高Topo Ⅱ基因的表达量(P<0.01)。结论 QGY7702/Sora细胞MRP、GST-π和Topo Ⅱ的表达水平与亲本细胞无显著差异。耐药细胞对Sorafenib敏感性降低与MRP、GST-π过表达相关,而益气化瘀解毒方拮抗Sorafenib耐药与抑制GST-π过表达相关。Objective To explore the effect of Yiqi Huayu Jiedu Prescription on the proliferation and expressionof MRP,GST-π and Topo II genes of sorafenib acquired drug-resistant human hepatocarcinoma QGY7702 cells (QGY7702/Sora).Methods QGY7702/Sora cells and QGY7702 cells were cultured.Cell Counting Kit-8 (CCK-8) method was used to detect the half inhibition rate (IC50) of Sorafenib on cells and calculate the resistance indexRI.To observe the effect of Yiqi Huayu Jiedu prescription on the proliferation of drug-resistant cells,and to detectthe expression levels of MRP,GST-π and Topo II genes in the two kinds of cells before and after drug intervention by fluorescence quantitative PCR.Results The IC50 values of parent cells and drug-resistant cells Sorafenib were (7.993±0.522) μmol/L and (19.651±1.216) μmol/L,and RI was about 2.5.Yiqi Huayu Jiedu prescription can inhibitthe proliferation of drug-resistant cells.Compared with parental cells,there was no significant difference in MRP,GST-π and Topo II expression in drug-resistant cells (P>0.05).Sorafenib group could promote the overexpressionof MRP and GST-π genes in drug-resistant cells (P<0.05),Yiqi Huayu Jiedu Prescription group could inhibit theoverexpression of GST-π gene (P<0.01),and combined with Sorafenib could significantly increase the expression ofTopo II gene (P<0.01).Conclusion There was no significant difference in MRP、GST-π and Topo II expression levelsbetween QGY7702/Sora cells and parent cells.The decreased sensitivity of drug-resistant cells to Sorafenib wasrelated to the over-expression of MRP and GST-π,while the antagonism of Yiqi Huayu Jiedu prescription to Sorafenibresistance was related to the inhibition of GST-π over-expression.

关 键 词：Sorafenib获得性耐药 MRP GST-Π TopoⅡ 益气化瘀解毒方 

分 类 号：R735.7[医药卫生—肿瘤]