Zhang Kai Guang, Qin Cheng Yong, Wang Hui Qun, Wang Jun Xian, Wang Qiao Min
Department of Gastroenterology, Shandong University School of Medicine, Jinan, Shandong Province, China.
Hepatogastroenterology. 2012 Nov-Dec;59(120):2672-6. doi: 10.5754/hge11850.
BACKGROUND/AIMS: To investigate the effect of tumor necrosis factor related apoptosis inducing ligand(TRAIL) on the expression of multidrug resistant genes MDR1, LRP and GST-n in drug-resistant gastric cancer cell strain SGC7901/VCR, and discuss a potential mechanism that reverses the multidrug resistance of gastric cancer with TRAIL as the target point.
SGC7901/VCR cell strain was treated over 48 h with TRAIL (50, 100, 200 and 400ig/L, respectively). The expression ofMDR1, LRP, GST-r mRNA in different groups of gastric cell strains was tested by RT-PCR and the expression of P-gp, LRP and GST-n by ELISA.
Under the action of TRAIL of different concentrations, different degrees of inhibition were observed in the expression of the mRNA and protein, and the difference from the reference group was statistically significant(p<0.01). Except for the insignificant inhibition degree of mRNA and protein in MDR1, LRP and GST-nr as compared between the 400lg/L and the 2001ig/L group(p>0.05), the differences between other groups were all statistically significant (p<0.05).
As preliminarily estimated from the results of the study, TRAILis negatively correlated with drug-resistant genes. It is possible that TRAIL increases the apoptosis and growth inhibition of chemotherapy drug tumor cells by reducing the expression of drug-resistant genes MDR1, LRP and GST-Tt, thereby participating in the reversion of the multidrug resistance of gastric cancer
背景/目的:探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)对耐药胃癌细胞株SGC7901/VCR中多药耐药基因MDR1、LRP和GST-π表达的影响,并以TRAIL为靶点探讨逆转胃癌多药耐药的潜在机制。
用TRAIL(分别为50、100、200和400μg/L)处理SGC7901/VCR细胞株48小时以上。采用RT-PCR检测不同组胃癌细胞株中MDR1、LRP、GST-π mRNA的表达,采用ELISA检测P-gp、LRP和GST-π的表达。
在不同浓度TRAIL作用下,mRNA和蛋白表达均出现不同程度的抑制,与对照组相比差异有统计学意义(p<0.01)。除400μg/L组与200μg/L组相比MDR1、LRP和GST-π mRNA及蛋白抑制程度无显著性差异(p>0.05)外,其他各组间差异均有统计学意义(p<0.05)。
根据本研究结果初步推测,TRAIL与耐药基因呈负相关。TRAIL可能通过降低耐药基因MDR1、LRP和GST-π的表达增加化疗药物对肿瘤细胞的凋亡和生长抑制作用,从而参与胃癌多药耐药的逆转。