人参皂苷Rg3对小鼠肺腺癌多耐药的逆转作用

Ginsenoside Rg3 reverses multidrug resistance of lung adenocarcinoma in mice

目的观察人参皂苷Rg3对小鼠肺腺癌多耐药的逆转作用并探讨其机制。方法 将32只接种获得性多药耐药Lewis肺癌细胞的小鼠随机分成4组:荷瘤对照组、多柔比星(ADM)组、人参皂苷Rg3组和人参皂苷Rg3联合多柔比星(ADM)组。各组予以相应干预,观察肿瘤生长情况,肿瘤接种24天处死全部小鼠,剥取皮下移植肿瘤,称瘤重,计算抑瘤率,收集移植瘤标本行免疫组织化学检测P-糖蛋白(P-glycaprotein,p-Gp)和多药耐药相关蛋白1的表达,并行RT-PCR半定量检测多药耐药基因(multidrug resistance,MDR1)mRNA、多药耐药相关蛋白1(multidrug resistance-associated protein 1,MRP1)mRNA表达。结果 (1)各用药组肿瘤的生长受到不同程度抑制,瘤重低于对照组,其抑瘤率分别为10.5%、36.3%、56.2%,联合用药组抗瘤作用进一步增强。(2)免疫组织化学:p-Gp及MRPl蛋白质的表达具有一致性,对照组和ADM组表达较高,而人参皂苷Rg3组和联合组表达明显降低,其中对照组和ADM组比较,人参皂苷Rg3组和联合组比较,差异无统计学意义(P>0.05);而人参皂苷Rg3组和联合组与对照组和ADM组比较差异均有统计学意义(P<0.01)。(3)RT-PCR:与对照组和ADM组比较,人参皂苷Rg3组和联合组MDR1 mRNA荧光强度降低,人参皂苷Rg3组、联合组同对照组及ADM组比较MDR1 mRNA相对量减小,差异均有统计学意义(P<0.01),而对照组同ADM组比较,人参皂苷Rg3组同联合组比较差异未见统计学意义,MRP1 mRNA的表达与MDR1 mRNA类似。结论 人参皂苷Rg3对小鼠肺腺癌多药耐药有逆转作用,其作用机制可能是下调MDR1 mRNA、MRP1 mRNA及其蛋白的表达。

Objective To investigate the reversal effect of ginsenoside-Rg3 （PG-Rg3） on muhidrug resistance of lung in mice. Methods Thirty-two mice bearing Lewis lung carcinoma multidrug-resistant cell line were randomized into four groups： control group, ADM group, PG-Rg3 group, ADM ＋ PG-Rg3 group. Mice in each group received appropriate intervention and the tumor growth was observed. All mice were sacrificed 24d after tumor inoculation, tumor weight was measured and the inhibitory rate was calculated; the expression of P-glycoprotein （p-Gp） and muhidrug resistance associated protein-1 （MRP-1） in tumor tissue was detected by immunohistochemistry; the expression of MDR1 mRNA and MRP1 mRNA was detected by RT-PCR. Results The tumor weight of ADM,PG-Rg3 and ADM ＋ PG-Rg3 groups was lower than that of control group. The inhibition rates were 10.5% ,36.3% and 56.2%, respectively. The expression of p-Gp and MRP1 proteins in PG-Rg3 and PG-Rg3 ＋ ADM groups was significantly lower than that in control and ADM groups （ P 〈 0.01 ）. The expression of MDR1 mRNA and MRP1 mRNA in PG-Rg3 and PG-Rg3 ＋ ADM groups was significantly lower than that in control and ADM groups （ P 〈 0.01 ）. Conclusion Ginsenoside-Rg3 can moderately reverse the multidrug resistance of lung adenocarcinoma in mice, which may be associated with the down-regulation of MDR1 mRNA, MRP1 mRNA,p-Gp and MRP1 proteins.