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Pokemon基因表達(dá)與胃癌耐藥性的關(guān)系

發(fā)布時(shí)間:2019-02-15 13:00
【摘要】:目的探討pokemon基因表達(dá)與胃癌細(xì)胞藥敏性及耐藥基因的關(guān)系。方法取60例胃癌組織和癌旁組織石蠟標(biāo)本,采用免疫組化技術(shù)檢測組織中pokemon蛋白及耐藥相關(guān)蛋白P-糖蛋白(P-gp)、多藥耐藥相關(guān)蛋白1(MRP1)、肺耐藥蛋白(LRP)、生存素(survivin)的表達(dá),并分析pokemon蛋白與其他4種蛋白的關(guān)系。采用磺酰羅丹明B(SRB)蛋白染色法檢測5-氟尿嘧啶(5-FU)、順鉑(DDP)、奧沙利鉑(L-OHP)對(duì)胃癌細(xì)胞株SGC7901、胃癌耐藥細(xì)胞株SGC7901/ADR、胃上皮細(xì)胞株GES-1的抑制作用;qPCR及蛋白質(zhì)印跡法檢測上述3種細(xì)胞株中pokemon和耐藥基因的表達(dá)。合成針對(duì)pokemon的siRNA并轉(zhuǎn)染SGC7901/ADR細(xì)胞,檢測轉(zhuǎn)染前后SGC7901/ADR細(xì)胞的化療藥敏性及耐藥基因的變化。結(jié)果胃癌組織中pokemon、P-gp、MRP1、LRP、survivin蛋白的陽性表達(dá)率均高于癌旁組織(P0.05);pokemon蛋白表達(dá)與P-gp、survivin蛋白表達(dá)間存在正相關(guān)關(guān)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細(xì)胞株中的表達(dá)高于細(xì)胞株SGC7901及GES-1;SGC7901/ADR細(xì)胞株的耐藥性最強(qiáng),SGC7901次之,GES-1最弱(P0.01)。Pokemon-siRNA轉(zhuǎn)染SGC7901/ADR細(xì)胞后細(xì)胞中pokemon mRNA的表達(dá)明顯受到抑制;轉(zhuǎn)染后化療藥物對(duì)細(xì)胞的抑制能力增強(qiáng),P-gp、survivin表達(dá)減弱(P0.05)。結(jié)論 Pokemon與P-gp、survivin通過相互調(diào)控而促進(jìn)胃癌耐藥性的形成。Pokemon可能成為胃癌靶向治療的候選基因。
[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.
【作者單位】: 河北醫(yī)科大學(xué)第四醫(yī)院外三科;
【基金】:國家自然科學(xué)基金(81372580) Supported by National Natural Science Foundation of China(81372580) 河北省自然科學(xué)基金(H2016206173) Natural Science Foundation of Hebei Province(H2016206173) 河北省衛(wèi)生和計(jì)劃生育委員會(huì)重點(diǎn)科技研究計(jì)劃項(xiàng)目(20150352) Key Program of Science and Technology Research of Health and Family Planning Commission of Hebei(20150352)
【分類號(hào)】:R735.2

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