靶向抑制COX-2基因对胃癌细胞BGC823凋亡及药物敏感性的影响

发布时间：2018-04-21 02:36

本文选题：COX- + WNT　；参考：《现代肿瘤医学》2016年03期

【摘要】：目的:研究siRNA靶向抑制环氧合酶-2(COX-2)基因后对胃癌细胞BGC823增殖、凋亡及药物敏感性的影响。方法:将COX-2 siRNA(siRNA-COX-2组)及negative control siRNA(siRNA-control组)序列转入细胞BGC823中,检测细胞增殖能力,观察多西紫杉醇(docetaxel艾素)、奥沙利铂(L-OHP)、5-氟尿嘧啶(5-FU)的药物敏感性变化,及转染前后BGC823细胞COX-2、β-catenin、Bcl-2 mRNA基因和蛋白的表达。结果:siRNA-COX-2组细胞在转染后第四天开始增殖能力下降,与siRNA-control组差异存在明显统计学意义(P0.05),而siRNA-control组细胞于BGC823组增殖能力差异无明显统计学意义(P0.05)。MTT法检测转染后胃癌细胞对艾素、奥沙利铂、5-氟尿嘧啶的IC50较转染前药物敏感性明显增加。流式细胞术检测转染前后胃癌细胞凋亡率为(3.08%±0.27%vs 16.14%±1.89%,P0.05),转染后凋亡明显增加(P0.05)。qRT-PCR法检测发现转染后COX-2、β-catenin、Bcl-2 mRNA基因的表达明显下降,Western blot检测发现,转染后48小时COX-2蛋白表达达到最低,转染后48小时β-catenin、Bcl-2蛋白表达明显下降(P0.05)。结论:通过下调COX-2基因的表达,可有效抑制WNT信号通路的激活,同时有效降低Bcl-2基因的表达。抑制COX-2基因后可有效降低胃癌细胞BGC823的细胞增殖能力,可有效提高对艾素、奥沙利铂、5-氟尿嘧啶的药物敏感性,有效促进细胞凋亡。
[Abstract]:Aim: to study the effects of siRNA targeting cyclooxygenase-2 cyclooxygenase-2 (COX-2) gene on the proliferation, apoptosis and drug sensitivity of gastric cancer cell line BGC823. Methods: the COX-2 siRNA(siRNA-COX-2 group and the negative control siRNA(siRNA-control group were transferred into the cell BGC823 to detect the proliferative ability of the cells, and to observe the drug sensitivity of docetaxel, oxaliplatin and 5-fluorouracil in docetaxel, oxaliplatin, 5-fluorouracil (5-FU). And the expression of Bcl-2 mRNA gene and protein in BGC823 cells before and after transfection. Results after transfection, the proliferation ability of the cells in the fraction siRNA-COX-2 group began to decrease on the fourth day after transfection, which was significantly different from that in the siRNA-control group (P 0.05), but there was no significant difference between the siRNA-control group and the BGC823 group. The sensitivity of oxaliplatin 5-fluorouracil (5-fluorouracil) in IC50 was significantly higher than that before transfection. The apoptotic rate of gastric cancer cells was 3.08% 卤0.27%vs 16.14% 卤1.89 before and after transfection by flow cytometry. After transfection, the expression of COX-2 protein reached the lowest at 48 hours after transfection. At 48 hours after transfection, the expression of 尾 -catenin B 2 protein decreased significantly (P 0.05). Conclusion: by down-regulating the expression of COX-2 gene, the activation of WNT signaling pathway and the expression of Bcl-2 gene can be effectively inhibited. Inhibition of COX-2 gene can effectively reduce the proliferation of gastric cancer cell line BGC823, can effectively enhance the drug sensitivity to oxaliplatin 5-fluorouracil, and promote cell apoptosis.
【作者单位】：兰州军区兰州总医院;胶州市人民医院;
【基金】：国家科技部、财政部科技惠民计划(编号:2012GS620101) 甘肃省科技厅科技重大专项资助项目(编号:2010GS04390)
【分类号】：R735.2

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