| 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（P<0.05）；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（P<0.01）。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（P<0.05）。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。 |
| 关键词: 胃肿瘤 pokemon 药物敏感性 多药耐药相关蛋白质类 |
| DOI：10.16781/j.0258-879x.2017.08.1034 |
| 投稿时间：2017-02-28修订日期：2017-06-11 |
| 基金项目:国家自然科学基金（81372580），河北省自然科学基金（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）. |
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| Relationship between pokemon gene expression and drug resistance of gastric carcinoma |
| JIA Nan,LI Yong*,FAN Li-qiao,TAN Bi-bo,LIU Yu,ZHANG Zhi-dong |
(Department of General Surgery (Ⅲ), Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China
*Corresponding author) |
| Abstract: |
| Objective To explore the relationship of pokemon gene expression and drug sensitivity and drug resistance gene in gastric cancer cells. Methods We collected the paraffin specimen of gastric cancer and para-carcinoma tissues from 60 patients with gastric cancer, detected the protein expressions of pokemon, drug resistance-associated protein P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), lung resistance protein (LRP) and survivin with immunohistochemistry (IHC) and analyzed the relationship between pokemon protein and other 4 proteins. Sulphorhodamine B (SRB) protein staining assay was performed to detect the inhibition effect of 5-fluorouracil (5-FU), cisplatin (DDP) and oxaliplatin (L-OHP) on gastric cancer cell line SGC7901, multidrug-resistant gastric carcinoma cell line SGC7901/ADR and gastric epithelial cell line GES-1, and qPCR and Western blotting were used to test expression of pokemon and drug resistance genes in the cells. Pokemon-siRNA was established and transfected into SGC7901/ADR cells, and the drug sensitivity and drug resistance genes were analyzed. Results Positive rates of pokemon, P-gp, MRP1, LRP and survivin proteins were significantly higher in gastric cancer tissues than those in para-carcinoma tissues (P<0.05). The protein expression of pokemon was positively correlated with P-gp and survivin (r=0.385 2, P=0.002; r=0.342 4, P=0.007). Protein expressions of pokemon, P-gp, MRP1, and survivin were higher in SGC7901/ADR cells than those in SGC7901 and GES-1 cells. The drug resistance of SGC7901/ADR cells was the strongest, followed by SGC7901, and that of GES-1 was the weakest (P<0.01). After SGC7901/ADR cells was transfected with pokemon-siRNA, pokemon mRNA expression was significantly inhibited, mRNA and protein expressions of P-gp and survivin were decreased and the inhibitory effect of chemotherapy agents on SGC7901/ADR cells was increased (P<0.05). Conclusion The pokemon is involved in drug resistance of gastric cancer by mutual regulation with P-gp and survivin, and pokemon may be a candidate gene for gastric cancer targeted treatment. |
| Key words: stomach neoplasms pokemon drug sensitivity multidrug resistance-associated protein |
