背景与目的:研究发现锌指蛋白139(ZNF139)在胃癌中表达异常,但ZNF139与胃癌的多药耐药性(multidrugresistance,MDR)关系尚不明确。本研究检测了人胃癌细胞株SGC7901和耐药细胞株SGC7901/ADR中ZNF139和MRP-1、MDR1/P-gp、GST-π的mRNA和蛋白表达情况,并对其表达关系和意义进行分析。方法:体外培养SGC7901、SGC7901/ADR,逆转录-聚合酶连反应(reverse transcription-polymerase chain reaction, RT-PCR)检测两种细胞ZNF139和MRP-1、MDR1/P-gp、GST-πmRNA表达情况,采用蛋白质印迹法(Western blot)法检测各基因蛋白表达变化情况。合成针对ZNF139的小干扰RNA(siRNA-ZNF139)重组质粒并转染SGC7901/ADR,检测转染前后SGC7901/ADR中MRP-1、MDR1/P-gp、GST-π表达的变化。结果:SGC7901和SGC7901/ADR两种细胞中均有ZNF139、MRP-1、MDR1/P-gp、GST-πmRNA和蛋白阳性表达,SGC7901/ADR细胞中ZNF139、MRP-1、MDR1/P-gp、GST-πmRNA和蛋白表达均明显高于SGC7901细胞(P<0.05)。转染siRNA-ZNF139后SGC7901/ADR细胞中ZNF139表达明显受到抑制,MRP-1、MDR1/P-gp、GST-π表达也明显降低(P<0.05)。结论:ZNF139通过上调MRP-1、MDR1/P-gp、GST-π基因表达而参与胃癌多药耐药形成。%Background and purpose:It was reported that zinc ifnger protein 139 (ZNF139) was expressed aberrantly in gastric cancer. But the relationship between ZNF139 and multidrug resistance (MDR) of gastric cancer is still not clear. The purpose of this research was to investigate the expressions and signiifcance of ZNF139, MRP-1, MDR1/P-gp, GST-π in human gastric carcinoma cell lines SGC7901 and SGC7901/ADR. Methods: The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere determined with RT-PCR and Western blot in SGC7901 and SGC7901/ADR cell lines. Then siRNA recombinant plasmid of targeting ZNF139 gene was constructed and imported into gastric cancer cell line SGC7901/ADR, and the expressions of MRP-1, MDR1/P-gp, GST-πwere tested simultaneously. Results:The expressions of ZNF139, MRP-1, MDR1/P-gp, GST-πwere higher in SGC7901/ADR than in SGC7901(P<0.05). ZNF139 was inhibited obviously after siRNA-ZNF139 was transfected into SGC7901/ADR, and expression of MRP-1, MDR1/P-gp, GST-πdecreased(P<0.05). Conclusion:ZNF139 may be invovled in multidrug resistance (MDR) of gastric cancer by up-regulating MRP-1, MDR1/P-gp and GST-π.
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