TRAIL抑制胃癌多药耐药基因MDR1/P-gp的表达

目的观察肿瘤坏死因子相关凋亡诱导配体(TRAIL)对胃癌耐药细胞株SGC-7901/VCR多药耐药基因MDR1及其编码P-gp蛋白表达的影响,探讨以TRAIL为靶点逆转胃癌多药耐药的机制。方法 SGC-7901/VCR细胞株经不同浓度的TRAIL处理48 h后,RT-PCR检测各组胃癌细胞株中多药耐药MDR1 mRNA的表达情况,同时用ELISA法检测各组胃癌细胞株中P-gp表达的含量。结果不同浓度TRAIL(50、100、200、400μg/L)作用于细胞后,胃癌耐药细胞株SGC-7901/VCR的MDR1/P-gp表达受不同程度抑制,与对照组相比差异均具有统计学意义(P<0.05)。400μg/L与200μg/L组相比其MDR1/P-gp抑制程度并不明显,其余各组间差异均有统计学意义(P<0.05)。结论 TRAIL可抑制SGC-7901/VCR MDR1/P-gp的表达,且呈量效关系。TRAIL可能通过降低耐药基因MDR1的表达逆转胃癌的多药耐药。

TRAIL down-regulates the expression of multidrug resistance gene MDR1 and P-gp in gastric cancer cells

Objective To observe the effect of tumor necrosis factor related apoptosis inducing ligand(TRAIL)to down-regulate the expression of multidrug resistance gene MDR1 and P-gp protein in the gastric cancer cell SGC-7901/VCR and investigate the mechanism of TRAIL as a target of reversing multidrug resistance of gastric cancer.Methods SGC-7901/VCR cells were treated with TRAIL in different concentrations(50,100,200,400 μg/L) respectively.48 h later,the expression of MDR1 mRNA were detected by RT-PCR,P-gp protein expression in SGC-7901/VCR cells was detected by ELISA.Results Different concentrations of TRAIL(50,100,200,400 μg/L) treated the cells,the expression of MDR1 and P-gp were inhibited by different concentrations,compared with the control group,there were statistically significant differences(P<0.05).400 μg/L TRAIL compared to 200 μg/L TRAIL,the inhibition of MDR1 and P-gp was not significantly difference,the other groups were statistical differences(P<0.05).Conclusions TRAIL can inhibit the expression of MDRL/P-gp in a dose dependent manner.It suggests that TRAIL may play a potential role in overcoming the chemotherapeutic resistance of gastric cancer cells through down-regulate the expression of multidrug resistance gene(mDR1).