丹参酮ⅡA对小鼠S180肿瘤获得性多药耐药及P-gp、LRP的影响

Effect of tanshinone ⅡA on acquired multi-drug resistance of S180's tumor and expression of P-gp,LRP and TOPOⅡ in mice

目的观察丹参酮ⅡA对化疗诱导的小鼠S-180肿瘤获得性多药耐药(MDR)模型化疗敏感性、细胞凋亡及对P-糖蛋白(P-gp)、肺癌耐药蛋白(LRP)、拓扑异构酶Ⅱ(TOPOⅡ)表达的影响。方法复制小鼠S-180MDR实体瘤模型,随机分为环磷酰胺(CTX)组、丹参酮ⅡA+CTX组、丹参酮ⅡA组、MDR模型组,连续给药4周,观察各组瘤体大小,计算抑瘤率。复制小鼠S-180MDR腹水癌模型,随机分为模型组、CTX组、CTX+丹参酮ⅡA组,给予药物4周后,流式细胞仪观察干预后各组细胞凋亡率、P-gp、LRP、TOPOⅡ变化。结果丹参酮ⅡA+CTX组抑瘤率较CTX组显著增高,差异有统计学意义(P<0.01);丹参酮ⅡA+CTX组细胞凋亡率较CTX组显著增高,而P-gp、TOPOⅡ、LRP表达率较CTX组显著降低,差异均有统计学意义(P<0.01)。结论丹参酮ⅡA有逆转小鼠S-180肿瘤获得性多药耐药的作用,可能与降低P-gp、LRP、TOPOⅡ表达有关。

Objective To observe the influence of Tanshinone ⅡA on acquired multi-drug resistance（MDR） model chemosensitivity,Apoptosis,P-glycoprotein（P-gp）,lung cancer resistance protein（LCR） and Topoisomerase Ⅱ（TOPOⅡ） in MDR mice with S180＇s tumor.Methods The mice,induced as the S-180 MDR mouse model,were randomly divided into CTX,Tanshinone ⅡA＋CTX,tanshinone ⅡA and MDR model groups,and treated 4 weeks,then,the sizes of tumor were measured and the tumor inhibitory rate was counted.The mouse S180＇s ascites tumor model was established,randomly divided into model,CTX,CTX ＋tanshinone ⅡA groups,treated 2 weeks,the apoptosis rates of tumor cells were measured with flow cytometry and the change of P-gp,LRP and TOPOⅡ with fluorescence detection.Results The tumor inhibitory rate in CTX ＋Tanshinone ⅡA group were significant higher than that in CTX group（P0.01）;The apoptosis rate of tumor cell in CTX ＋Tanshinone ⅡA group was significant higher than that in CTX group,and the expression of P-gp,LRP and TOPO Ⅱ in CTX＋Tanshinone ⅡA group were significant lower that that in CTX group（P0.01）.Conclusion Tanshinone ⅡA can reverse the acquired MDR of mouse S180 tumor.which may have some relate to the decreasing of P-gp,LRP and TOPOⅡ.