消岩汤对耐顺铂人肺腺癌A549/DDP细胞多药耐药相关蛋白的调控作用

目的探讨消岩汤含药血清对耐顺铂人肺腺癌A545659/DDP细胞多药耐药相关蛋白1(MRP1)、肺耐药蛋白(LRP)及其m RNA表达水平的影响,发现消岩汤对化疗耐药的作用靶点,为肺癌化疗耐药的临床治疗提供理论基础。方法 A549裸鼠皮下移植瘤模型ip给予等量生理盐水,2 mg/kg顺铂,消岩汤低、高剂量(20、40 g/kg)获得含药血清,选择耐顺铂人肺腺癌A549/DDP细胞系作为获得性耐药模型,采用Western blotting免疫印迹法及RT-PCR技术,检测各组含药血清作用下A549/DDP细胞多药耐药基因MRP1、LRP及其产物MRP1、LRP蛋白的表达水平。结果与对照组相比,随着血清中药物浓度的增加,消岩汤低、高剂量组LRP与MRP1蛋白表达逐渐减弱(P0.05)。LRP及MRP1 m RNA水平也有所下降(P0.05),且随着药物浓度的增加,基因表达抑制越明显。结论不同浓度的消岩汤含药血清对MRP1、LRP及其m RNA表达均具有不同程度的抑制作用,且浓度越高,抑制作用越明显,即与剂量呈正相关,揭示消岩汤逆转肺癌耐药可能与抑制MRP1和LRP蛋白功能有关。

Research of Xiaoyan Decoction on multidrug resistance of lung adenocarcinoma A549/DDP cell with cisplatin resistance in human gene

Objective To study the Xiaoyan Decoction serum influence the expression level of lung adenocarcinoma that cisplatin-resistent of A549/DDP cell multidrug resistance-associated protein 1 (MRP1), lung resistance-related protein (LRP), MRP mRNA, and LRP mRNA, to find out Xiaoyan Decoction''s target to the chemotherapy resistance, and to lay foundation for the clinical of reversing lung cancer chemotherapy resistance. Methods The A549 nude mice hypodermic tumor model was given an equal amount of saline, 2 mg/kg of cisplatin, low and high doses of Xiaoyan Decoction (20, 40 g/kg), and then the serum was gain. The cisplatin resistance of human lung adenocarcinoma A549/DDP cell line was chosen as acquired drug-resistance model, Xiaoyan Decoction on MDR of A549/DDP cell gene expression product of multidrug resistance-associated protein 1, lung resistance-related protein and its effect on mRNA expression level was detected by Western blotting and RT-PCR technique. Results Compared with the control group, the expression of MRP1 and LRP protein decreased gradually (P < 0.05) as the serum drug concentration of Xiaoyan Decoction increased. The level of LRP mRNA and MRP1 mRNA in low and high doses of Xiaoyan Decoction group also decreased, and much more obvious inhibition of gene expression was observed as the increasing of drug concentration.Conclusion Different serum drug concentration of Xiaoyan Decoction can differently control the expression of MRP1, LRP protein, MRP1 mRNA, and LRP mRNA, with the increasing of serum drug concentration, the decreasing of expression level, namely positive-correlated to the dose, which indicates that Xiaoyan Decoction Reversal of the lung cancer drug resistance the might related to the MRP1 and LRP.