Ad-apoptin通过AMPK/ACC信号通路抑制肺癌细胞脂代谢  

Ad-apoptin inhibits lipid metabolism in lung cancer cells through AMPK/ACC signaling pathway

作　　者：宋高杰 尚超 李一权 朱羿龙[3] 金宁一(指导) 李霄(指导) SONG Gaojie;SHANG Chao;LI Yiquan;ZHU Yilong;JIN Ningyi;LI Xiao(Medical College,Yanbian University,Yanji 133002,China)

机构地区：[1]延边大学医学院,延吉133002 [2]中国农业科学院长春兽医研究所,长春130122 [3]长春中医药大学,长春130117

出　　处：《中国免疫学杂志》2022年第5期569-573,579,共6页Chinese Journal of Immunology

基　　金：吉林省自然科学基金(202101046JC);吉林省青年科技人才托举工程项目(QT202111)资助。

摘　　要：目的:探讨溶瘤腺病毒Ad-apoptin对非小细胞肺癌细胞脂代谢的影响及分子机制。方法:CCK-8法检测细胞活性;JC-1染色和Annexin V-FITC/PI检测细胞凋亡;Western blot检测脂代谢和凋亡相关蛋白;siRNA干扰肺癌细胞AMPK的表达;Co-IP检测Ad-apoptin与AMPK蛋白相互间作用;建立移植瘤小鼠模型,检测肿瘤的生长,并通过免疫组化检测TUNEL、Ki-67、p-AMPK和FASN蛋白表达量。结果:Ad-apoptin对肺癌细胞抑制率具有浓度依赖性(P<0.05),显著诱导细胞凋亡(P<0.05),降低细胞脂质累积,下调三酰甘油(TG)和总胆固醇(TC)含量,上调p-AMPK和p-ACC;敲低AMPK可显著减弱Ad-apoptin诱导的凋亡,而抑制ACC可显著增强Ad-apoptin诱导的凋亡。在体内试验中,Ad-apoptin能抑制体内肿瘤生长,同时也能抑制细胞增殖,并促进细胞凋亡。结论:Ad-apoptin以AMPK为靶点,通过AMPK/ACC途径,抑制肿瘤增殖和脂代谢并促进细胞凋亡。Objective:To investigate the effect of oncolytic adenovirus Ad-apoptin on lipid metabolism and apoptosis of non-small cell lung cancer cells and its molecular mechanism.Methods:CCK-8 was used to detect cell activity;JC-1 staining and Annexin V-FITC/PI were used to detect apoptosis;Lipid metabolism and apoptosis related proteins were detected by Western blot;siRNA interferes with the expression of AMPK;The interaction between Ad-apoptin and AMPK protein was detected by Co-IP;The transplanted tumor mouse model was established,the tumor growth was detected,and the expressions of TUNEL,Ki-67,p-AMPK and FASN were detected by immunohistochemistry.Results:Ad-apoptin significantly induced apoptosis(P<0.05),decreased cell lipid accumulation,(P<0.05)down regulated the contents of TG and TC,and up-regulated p-AMPK and p-ACC;knockdown of AMPK could significantly reduce Ad-apoptin induced apoptosis,while inhibition of ACC could significantly enhance Ad-apoptin induced apoptosis.In vivo,Ad-apoptin could inhibit tumor growth,inhibit cell proliferation and promote cell apoptosis.Conclusion:Ad-apoptin targets AMPK,inhibit tumor proliferation,lipid metabolism and promote apoptosis through AMPK/ACC pathway.

关 键 词：Ad-apoptin AMPK/ACC 肺癌 脂代谢 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤]