Pokemon基因表达与胃癌耐药性的关系

发布时间：2019-02-15 13:00

【摘要】：目的探讨pokemon基因表达与胃癌细胞药敏性及耐药基因的关系。方法取60例胃癌组织和癌旁组织石蜡标本,采用免疫组化技术检测组织中pokemon蛋白及耐药相关蛋白P-糖蛋白(P-gp)、多药耐药相关蛋白1(MRP1)、肺耐药蛋白(LRP)、生存素(survivin)的表达,并分析pokemon蛋白与其他4种蛋白的关系。采用磺酰罗丹明B(SRB)蛋白染色法检测5-氟尿嘧啶(5-FU)、顺铂(DDP)、奥沙利铂(L-OHP)对胃癌细胞株SGC7901、胃癌耐药细胞株SGC7901/ADR、胃上皮细胞株GES-1的抑制作用;qPCR及蛋白质印迹法检测上述3种细胞株中pokemon和耐药基因的表达。合成针对pokemon的siRNA并转染SGC7901/ADR细胞,检测转染前后SGC7901/ADR细胞的化疗药敏性及耐药基因的变化。结果胃癌组织中pokemon、P-gp、MRP1、LRP、survivin蛋白的阳性表达率均高于癌旁组织(P0.05);pokemon蛋白表达与P-gp、survivin蛋白表达间存在正相关关系(r=0.385 2,P=0.002;r=0.342 4,P=0.007)。Pokemon、P-gp、MRP1、survivin蛋白在SGC7901/ADR细胞株中的表达高于细胞株SGC7901及GES-1;SGC7901/ADR细胞株的耐药性最强,SGC7901次之,GES-1最弱(P0.01)。Pokemon-siRNA转染SGC7901/ADR细胞后细胞中pokemon mRNA的表达明显受到抑制;转染后化疗药物对细胞的抑制能力增强,P-gp、survivin表达减弱(P0.05)。结论 Pokemon与P-gp、survivin通过相互调控而促进胃癌耐药性的形成。Pokemon可能成为胃癌靶向治疗的候选基因。
[Abstract]:Objective to investigate the relationship between pokemon gene expression and drug sensitivity and drug resistance genes in gastric cancer cells. Methods pokemon protein, P- glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and lung resistance protein (LRP), were detected by immunohistochemical technique in 60 cases of gastric cancer and paracancerous tissues. The expression of survivin (survivin) and the relationship between pokemon protein and other four proteins were analyzed. Detection of 5-fluorouracil (5-FU) and cisplatin (DDP), oxaliplatin (L-OHP) in the treatment of gastric cancer cell line SGC7901, by using sulfonyl rhodamine B (SRB) protein staining to detect the effect of 5-fluorouracil (5-FU) and cisplatin (DDP), oxaliplatin (L-OHP) on SGC7901, cell line SGC7901/ADR, Inhibition of gastric epithelial cell line GES-1; QPCR and Western blot were used to detect the expression of pokemon and drug resistance genes. SiRNA targeting pokemon was synthesized and transfected into SGC7901/ADR cells. The chemosensitivity and drug resistance genes of SGC7901/ADR cells were detected before and after transfection. Results the positive expression rate of pokemon,P-gp,MRP1,LRP,survivin protein in gastric cancer tissues was higher than that in paracancerous tissues (P0.05). There was a positive correlation between the expression of); pokemon protein and the expression of P-gpP pokemon,P-gp,MRP1,LRP,survivin protein (r = 0.385 2, P = 0.002). The expression of Pokemon,P-gp,MRP1,survivin protein in SGC7901/ADR cell line was higher than that in SGC7901 and GES-1; cell line. The drug resistance of SGC7901/ADR cell line was the strongest, SGC7901 was the second, and GES-1 was the weakest (P0.01). The expression of pokemon mRNA was significantly inhibited after Pokemon-siRNA transfection into SGC7901/ADR cells. After transfection, the inhibitory effect of chemotherapeutic drugs on cells was enhanced, and the expression of P-gpP survivin was decreased (P0.05). Conclusion Pokemon and P-gpP survivin promote the formation of drug resistance in gastric cancer through mutual regulation. Pokemon may be a candidate gene for targeted therapy of gastric cancer.
【作者单位】：河北医科大学第四医院外三科;
【基金】：国家自然科学基金(81372580) Supported by National Natural Science Foundation of China(81372580) 河北省自然科学基金(H2016206173) Natural Science Foundation of Hebei Province(H2016206173) 河北省卫生和计划生育委员会重点科技研究计划项目(20150352) Key Program of Science and Technology Research of Health and Family Planning Commission of Hebei(20150352)
【分类号】：R735.2

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