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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 investigate the inhibitory effect of combination of DDP and DDP on the growth of subcutaneous xenografted lung cancer in nude mice with multi-drug-resistant lung cancer and its related mechanism. Methods To establish an animal model of lung adenocarcinoma xenograft tumor with stable drug resistance. Temperature below 0.2ml (containing crude drug 0.4g) / 10g body weight intragastric administration intervention. The effects of combination of cisplatin with cisplatin on the growth of xenografted nude mice were observed. The expression of mdr1 and mrp mRNA was detected by RT-PCR. The expression of mrp1 mRNA and protein was detected by immunohistochemistry The corresponding protein P-gp, mrp expression. Results Compared with cisplatin intervention group (DDP group), the body weight of nude mice bearing WMC + WDP + DDP group decreased more slowly (P <0.05), and the tumor volume and tumor weight decreased obviously. The tumor growth rate was slower (P <0.05). The relative expression of mdr1, mrpmRNA and P-gp, mrp proteins in the xenografts were significantly decreased (P <0.05). Conclusions Combination of warm and chemotherapeutic drugs can inhibit the growth of subcutaneous xenografts of multidrug-resistant lung cancer in nude mice. The mechanism may be related to decreasing the expression of mdr1 and mrp genes and proteins and enhancing the sensitivity of A549 / DDP to chemotherapeutics .