Effect and mechanisms of LINC00152 knockdown on chemotherapy resistance in mitomycin-resistant gastric cancer NCI-N87/MMC cells
- Author:
- No author available
- Journal Title:
- World Chinese Journal of Digestology
- Issue:
- 7
- DOI:
- 10.11569/wcjd.v29.i7.332
- Key Word:
- Linc00152;胃癌;NCI-N87细胞;丝裂霉素耐药;细胞凋亡
Abstract： 背景 长基因间非编码RNA 152(long intergenic noncoding RNA 152,Linc00152)在胃癌组织中高表达,且其能促进胃癌细胞增殖、迁移与侵袭,而Linc00152对胃癌化疗耐药的影响和机制并不清楚.目的 探究Linc00152对人胃癌细胞系NCI-N87化疗耐药性的影响及相关的作用机制.方法 实时定量荧光聚合酶链式反应(real-time fluorescence quantitative polymerase chain reaction,Real-time PCR)检测人胃癌细胞系NCI-N87及其丝裂霉素(mitomycin,MMC)耐药细胞系NCI-N87/MMC 中Linc00152的表达情况.采用小分子RNA干扰技术敲除NCI-N87/MMC中Linc001 52的表达后,MTT法检测细胞对MMC和顺铂的敏感性,流式细胞术检测细胞凋亡,Western Blot检测B细胞淋巴瘤/白血病-2(B cell lymphoma/lewkmia-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、半胱氨酸天冬氨酸蛋白酶-3(cysteine aspartic acid proteinase 3,caspase3)和劈裂的caspase3(cleaved-caspase3)的蛋白表达水平.此外,Real-time PCR和Western blot检测多药耐药蛋白1/P-糖蛋白(multidrug resistant protein 1/P-glycoprotein,MDR1/P-gp)、层粘连蛋白受体1前体抗原(P37-kDa laminin receptor-l precursor antigen,Mgrl-Ag)以及多药耐药相关蛋白(multidrug resistance-associated protein,MRP)的表达.结果 NCI-N87/MMC细胞中Linc00152的表达水平明显高于其亲本细胞NCI-N87.在NCI-N87/MMC细胞中,敲除Linc00152可诱导细胞凋亡,并增加其对MMC和顺铂的敏感性.敲除Linc00152可抑制NCI-N87/MMC细胞中Bcl-2蛋白表达,促进Bax蛋白表达和caspase 3的活化.此外,敲除Linc00152还可下调NCI-N87/MMC细胞中多药耐药基因MDR1、Mgr1-Ag、MRP及其编码的蛋白的表达.结论 下调NCI-N87/MMC细胞中Linc00152的表达可提高细胞对MMC和顺铂的敏感性,其机制可能与调控细胞凋亡相关因子促进凋亡,同时下调细胞中多药耐药基因MDR1、Mgr1-Ag及MRP的表达有关.
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