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目的探讨索拉非尼体外对人肝癌细胞(BEL-7402/FU)多药耐药性的逆转作用及可能机制。方法以MTT比色法测定索拉非尼对肝癌细胞的剂量效应曲线,并以流式细胞仪检测索拉非尼对肝癌细胞内罗丹明123(Rho123)浓度的影响,根据上述实验结果选取合适的索拉非尼实验剂量。以MTT法测定索拉非尼对抗癌药物细胞毒性的影响,用流式细胞仪检测细胞膜转运蛋白(P-gp)的表达,RT-PCR法检测mdr1基因的表达。结果索拉非尼浓度在4μmol/L时逆转效率较高且毒副作用较小,4μmol/L的索拉非尼能部分逆转BEL-7402/FU细胞的耐药性,对ADM、5-FU、GEM、DDP的逆转倍数分别为2.98、7.16、1.99、10.08倍,并可部分下调BEL-7402/FU细胞P-gp的表达,使mdr1基因表达与对照组相比下降了27.3%。结论索拉非尼具有体外逆转人肝癌细胞多药耐药性的作用,可能与下调mdr1基因表达、增加细胞内化疗药物的蓄积有关。
Objective To investigate the reversal effects of sorafenib on multidrug resistance in human hepatoma cells (BEL-7402 / FU) and its possible mechanism. Methods The dose-response curve of sorafenib on hepatoma cells was determined by MTT colorimetric method. The effect of sorafenib on the concentration of Rho123 in hepatocellular carcinoma cells was determined by flow cytometry. According to the above experimental results, Sorafenib experimental dose. The effects of sorafenib on the cytotoxicity of anti-cancer drugs were determined by MTT assay. The expression of P-gp was detected by flow cytometry. The expression of mdr1 gene was detected by RT-PCR. Results Sorafenib could reverse the drug resistance of BEL-7402 / FU cells in a dose-dependent manner at a concentration of 4μmol / L and less toxic side effects. Sorafenib (4μmol / L) GEM and DDP were 2.98,7.16,1.99,10.08 fold, respectively, and partially down-regulated the expression of P-gp in BEL-7402 / FU cells, resulting in a 27.3% decrease in mdr1 gene expression compared with the control group. Conclusion Sorafenib can reverse the multidrug resistance of human hepatoma cells in vitro, which may be related to the down-regulation of mdr1 gene expression and the accumulation of intracellular chemotherapeutic drugs.