水飞蓟素对缺氧人肝癌HepG-2细胞HIF-1α及MDR1表达的影响  

Effects of silymarin on HIF‑1α and MDR1 expression in HepG‑2 cells under hypoxia

作　　者：张健 彭勇 马海 杨柳 Zhang Jian;Peng Yong;Ma Hai;Yang Liu(Department of Hepatobiliary Surgery,Central Hospital of Nanchong,Nanchong 637000,Sichuan,China;Department of respiratory,Central Hospital of Nanchong,Nanchong 637000,Sichuan,China)

机构地区：[1]南充市中心医院肝胆外科,四川南充637000 [2]南充市中心医院呼吸内科,四川南充637000

出　　处：《肿瘤代谢与营养电子杂志》2021年第2期175-178,共4页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：川北医学院2018年市校战略合作科技专项资金(18SXHZ0435)。

摘　　要：目的探讨水飞蓟素(SM)对缺氧条件下人肝癌HepG-2细胞中缺氧诱导因子-1α(HIF-1α)和多耐药基因1(MDR1)表达的影响。法不同浓度的SM(0、10、20、40 mg/L)与浓度梯度的化疗药物(多柔比星、索拉菲尼、顺铂)处理HepG-2细胞后应用四甲基偶氮唑蓝比色法(MTT)检测不同浓度SM对HepG-2细胞化疗药物敏感性的影响;在缺氧条件下,分别用0、10、20、40 mg/L的SM处理HepG-2细胞8 h后,应用RT-PCR检测不同浓度SM对HepG-2细胞的HIF-1α及MDR1 mRNA表达水平的影响,利用蛋白质印迹法检测不同浓度SM对HepG-2细胞的HIF-1α及P-糖蛋白(P-Gp)蛋白表达水平的影响。结果随着SM浓度的增加,HepG-2细胞对化疗药物多柔比星、索拉菲尼和顺铂的敏感性逐渐增强;与对照组相比,10、20、40 mg/L SM处理的HIF-1αmRNA表达量差异无统计学意义(P>0.05),而MDR1 mRNA表达量呈浓度依赖性降低(P<0.05),10、20、40 mg/L SM处理的HIF-1α与P-Gp蛋白表达水平呈浓度依赖性降低(P<0.05)。结论SM可能通过在转录后水平抑制HepG-2细胞HIF-1α的蛋白表达而降低MDR1的mRNA与蛋白表达,从而降低肝癌细胞的耐药性。Objective To investigate the effect of silymarin(SM)on the expression of hypoxia-inducible factor-1 alpha(HIF-1α)and multidrug resistance 1(MDR1)in HepG-2 cells under hypoxia.Methods After treatment of HepG-2 cells with different concentrations of SM(0,10,20,40 mg/L)and concentration gradient chemotherapeutic drugs(doxorubicin,sorafenib,cisplatin),MTT assay was used to detect the effect of different concentrations of SM on the sensitivity of HepG-2 cells to chemotherapeutic drugs.Under hypoxic conditions,HepG-2 cells were treated with SM at 0,10,20,and 40 mg/L for 8 h,RTPCR was used to detect the effects of different concentrations of SM on the expression levels of HIF-1αand MDR1 mRNA,and Western Blot was used to detect the effects of different concentrations of SM on the protein expression levels of HIF-1αand Pglycoprotein(P-Gp)in HepG-2 cells.Results With the increase of SM concentration,the sensitivity of HepG-2 cells to the chemotherapy drugs doxorubicin,sorafenib and cisplatin gradually increased.Compared with the control group,there was no significant difference in HIF-1αmRNA expression in the 10,20,and 40 mg/L SM treatment groups(P>0.05),while the MDR1 mRNA expression decreased in a concentration-dependent manner(P<0.05).Additionally,the HIF-1αand P-Gp protein expression levels of the 10,20,and 40 mg/L SM treatment groups decreased in a concentration-dependent manner compared with the control group(P<0.05).Conclusion SM might reduce the expression of MDR1 by inhibiting the expression of HIF-1αin HepG-2 cells at the post-transcriptional level,thereby reducing the drug resistance of hepatocellular carcinoma cells.

关 键 词：水飞蓟素 HEPG-2细胞 缺氧诱导因子-1α 多耐药基因1 P-糖蛋白 

分 类 号：R285[医药卫生—中药学]