温下方联合顺铂对A549/DDP裸鼠移植瘤的抑制作用及对药物转运蛋白表达的影响

Inhibitory effect of WCF decoction combined with DDP on the growth of transplanted tumor in nude mice and expression of drug transporter

目的探讨温下方与顺铂(DDP)合用对肺癌多药耐药裸鼠模型皮下移植瘤生长的抑制作用及其相关机制。方法建立耐药特性稳定的肺腺癌移植瘤裸小鼠动物模型。温下方0.2ml(含生药0.4g)/10g体质量灌胃给药干预。观察温下方与顺铂合用对裸鼠移植瘤生长的影响;RT-PCR法检测多药耐药基因(mdr1)和多药耐药相关蛋白基因(mrp)mRNA表达;免疫组化法检测上述基因相应蛋白P-gp、mrp的表达。结果与顺铂干预组(DDP组)相比,温下方与顺铂联合应用组(WCF+DDP组)荷瘤裸鼠体重下降较慢(P<0.05),移植瘤体积和瘤重量明显下降,肿瘤生长速度较缓(P<0.05),移植瘤中mdr1、mrpmRNA及P-gp、mrp蛋白的相对表达量均显著降低,差异有统计学意义(P<0.05)。结论温下方与化疗药合用对肺癌多药耐药裸鼠皮下移植瘤生长具有抑制作用,其机制可能通过降低药物转运蛋白mdr1和mrp基因及蛋白表达,增强A549/DDP对化疗药物的敏感性有关。

Objective To observe the inhibitory effect of Wenxiachangfu(WCF) decoction combined with DDP on the growth of transplanted tumor of human lung adenocarcinoma in nude mice and the associated molecular mechanisms.Methods A multidrug resistant(MDR) model of human lung adenocarcinoma in nude mice was established.The mice received an administration of WCF decoction 0.2 ml/10 g.The growth of transplanted tumor was observed,the expression of multi-drug resistance1(mdr1) and multi-drug resistance-associated protein(mrp) mRNA and proteins were detected respectively by reverse transcriptase polymerase chain reaction(RT-PCR) and immunohistochemical method.Results Compared with DDP intervention group,the decrease of the weight of mice in WCF decoction combined with DDP group had slowed down(P<0.05),the volume and weight of transplanted tumor had declined significantly(P<0.05),the growth rate of tumor had slowed(P<0.05).The expression of mdr1,mrp mRNA and protein had significantly reduced(P<0.05).Conclusions WCF decoction combined with DDP have significant inhibitory effects on the growth of transplanted tumor in nude mice,and the mechanism may be related to the decrease of mdr1 and mrp mRNA and proteins expression.