莫诺苯宗对肺腺癌细胞自噬和凋亡的分子机制研究  

Molecular mechanism of monobenzone on autophagy and apoptosis in lung adenocarcinoma cells

作　　者：刘亚[1] 庞亚梅 李宏[1] 阳甜[1] 宁谦 任徽[1] LIU Ya;PANG Yamei;LI Hong;YANG Tian;NING Qian;REN Hui(Department of Respiratory and Critical Care Medicine,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院呼吸与危重症医学科,陕西西安710061

出　　处：《陕西医学杂志》2024年第7期879-883,共5页Shaanxi Medical Journal

基　　金：陕西省自然科学基础研究计划项目(2018JQ8044)。

摘　　要：目的:探究莫诺苯宗和自然杀伤细胞激活受体基因(KLRC3)对肺腺癌(LUAD)细胞凋亡和自噬的影响,为LUAD的治疗提供理论基础。方法:分别使用不同浓度莫诺苯宗处理LUAD细胞,并采用CCK-8法检测莫诺苯宗对LUAD细胞活力的影响;随后,使用80μmol/L的莫诺苯宗、50 nmol/L的KLRC3干扰质粒(si-KLRC3)、和100 nmol/L自噬抑制剂3-甲基腺嘌呤(3-MA)1.5μg/ml KLRC3过表达载体(pcDNA-KLRC3)处理细胞后采用流式细胞术和Western blotting检测细胞凋亡以及凋亡相关蛋白和自噬相关蛋白的表达量。结果:莫诺苯宗浓度大于20μmol/L时可有效减弱LUAD细胞活力,且以剂量依赖性地促进了LUAD细胞的凋亡和自噬(均P<0.05)。KLRC3在LUAD细胞中低表达,干扰KLRC3减弱了莫诺苯宗对LUAD细胞自噬和凋亡的促进作用,比较差异有统计学意义(均P<0.05)。此外,过表达KLRC3也促进了LUAD细胞的凋亡和自噬,而KLRC3和莫诺苯宗对LUAD细胞凋亡和自噬的促进作用均可被3-MA所抵消,比较差异有统计学意义(均P<0.05)。结论:莫诺苯宗可能通过促进KLRC3的表达诱导自噬进而促进LUAD细胞的凋亡。Objective:To explore the effects of monobenzone and natural killer cell activating receptor gene(KLRC3)on apoptosis and autophagy of lung adenocarcinoma(LUAD)cells,and to provide a theoretical basis for the treatment of LUAD.Methods:The LUAD cells were treated with different concentrations of monobenzone,and the effect of monobenzone on the viability of LUAD cells was detected by CCK-8 method.Subsequently,the LUAD cells were treated with 80μmol/L monobenzone,50 nmol/L KLRC3 interference plasmid(si-KLRC3),100 nmol/L autophagy inhibitor 3-methyladenine(3-MA),and 1.5μg/ml KLRC3 overexpression vector(pcDNA-KLRC3).Then,flow cytometry and Western blot were used to detect apoptosis and the expression of apoptosis-related proteins and autophagy-related proteins.Results:The results showed that when the concentration of monobenzone was greater than 20μmol/L,it could effectively reduce the viability of LUAD cells and promote the apoptosis and autophagy of LUAD cells in a dose-dependent manner(all P<0.05).The expression of KLRC3 was downregulated in LUAD cells.Knockdown of KLRC3 attenuated the promotion of monobenzone on autophagy and apoptosis in LUAD cells(all P<0.05).In addition,overexpression of KLRC3 also promoted the apoptosis and autophagy of LUAD cells,while the promotion of KLRC3 and monobenzone on the apoptosis and autophagy of LUAD cells could be offset by 3-MA(all P<0.05).Conclusion:This study shows that monobenzone may induce autophagy by promoting the expression of KLRC3 and promote the apoptosis of LUAD cells.

关 键 词：肺腺癌 莫诺苯宗 自然杀伤细胞激活受体基因 自噬 细胞凋亡 细胞活力 

分 类 号：R-33[医药卫生]