高压氧通过MAPK信号通路增强长春新碱对胃癌细胞的增殖抑制作用研究  

Hyperbaric oxygen enhances the inhibitory effect of vincristine on the proliferation of gastric cancer cells through the MAPK signaling pathway

作　　者：王坤[1] 刘博 Wang Kun;Liu Bo(Department of Gastrointestinal and Hepatobiliary Surgery,Shangqiu First People's Hospital,Shangqiu 476100,China;Jilin Cancer Hospital,the Second Department of Colorectal Surgery,Changchun 130000,China)

机构地区：[1]商丘市第一人民医院胃肠肝胆外科,商丘476100 [2]吉林省肿瘤医院结直肠外二科,长春130000

出　　处：《中华内分泌外科杂志(中英文)》2025年第1期115-119,共5页Chinese Journal of Endocrine Surgery

基　　金：2018年度河南省医学科技攻关计划(2018020941)。

摘　　要：目的:探索0.2MPa高压氧(HBO)是否能增强长春新碱(VCR)对胃癌AGS细胞的增殖抑制作用、诱导凋亡作用并探索其相关分子机制。方法:建立胃癌AGS/VCR耐药细胞系;利用CCK-8实验检测HBO及VCR联用对AGS/VCR细胞增殖的影响;利用Hochest/PI双染法和流式细胞术检测HBO及VCR联用对AGS/VCR细胞凋亡的影响;利用Western blot检测细胞凋亡相关蛋白及通路蛋白的表达量。结果:CCK-8结果显示HBO与VCR联用能有效逆转AGS/VCR细胞对VCR耐药作用;Hochest/PI染色实验显示联用后细胞出现明显凋亡的形态;流式细胞术和凋亡蛋白的检测结果进一步表明联用后细胞凋亡大幅增加,与VCR单独处理组相比差异具有统计学意义;Western blot实验表明,HBO及VCR联用可激活p38/ERK信号通路并抑制AGS/VCR细胞中P-gp、MRP蛋白的表达。结论:HBO与VCR联用增强AGS/VCR细胞对VCR的敏感性并诱导细胞凋亡,其机制可能与联用后调控p38/ERK信号通路和耐药相关蛋白有关。Objective:To explore whether 0.2 MPa hyperbaric oxygen(HBO)can enhance the proliferation inhibitory effect of vincristine(VCR)on gastric cancer AGS cells,induce apoptosis,and explore its related molecular mechanisms.Methods:Gastric cancer AGS/VCR drug-resistant cell line was established.CCK-8 experiment was carried to detect the effect of HBO and VCR on the proliferation of AGS/VCR cells.Hochest/PI double staining method and flow cytometry were used to detect the effect of HBO and VCR on AGS/VCR cell apoptosis.Western blot was used to detect the expression of apoptosis-related proteins and pathway proteins.Results:CCK-8 results showed that the combination of HBO and VCR can effectively reverse the resistance of AGS/VCR cells to VCR.Hochest/PI staining experiment showed the cells revealing obvious apoptotic morphology after combined use.The detection results of flow cytometry and apoptotic protein further showed that cell apoptosis increased significantly after the combined use,which was statistically different compared with that of ethe VCR alone treatment group.Western blot experiments showed that the combination of HBO and VCR activated the p38/ERK signaling pathway and inhibited the expression of P-gp and MRP proteins in AGS/VCR cells.Conclusions:The combination of HBO and VCR enhances the sensitivity of AGS/VCR cells to VCR and induces apoptosis.The mechanism may be related to the regulation of p38/ERK signaling pathway and drug resistance-related proteins after the combination.

关 键 词：高压氧 胃癌细胞 细胞凋亡 p38/ERK信号通路 长春新碱耐药性 

分 类 号：R735.2[医药卫生—肿瘤]