美洲大蠊提取物体外对肝癌耐药细胞BEL-7402/5-FU自噬和侵袭转移的影响  

Effects of Extracts from Periplaneta americana L.on Autophagy,Invasion and Metastasis of Hepatocarcinoma Drug-Resistant Cells BEL-7402/5-FU in vitro

作　　者：马璟婷 周杰 李彩琳 吴定宇 彭芳 MA Jingting;ZHOU Jie;LI Caiin;WU Dingyu;PENG Fang(College of Pharmacy,Dali University,Dali 671000,China;Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D,Dali China)

机构地区：[1]大理大学药学院,云南大理671000 [2]云南省昆虫生物医药研发重点实验室,云南大理671000

出　　处：《中医药信息》2023年第12期23-28,34,共7页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81560600)。

摘　　要：目的:探讨美洲大蠊提取物CⅡ-3和脱脂膏对肝癌耐5-氟尿嘧啶细胞(BEL-7402/5-FU)自噬和转移侵袭能力的影响。方法:以肝癌敏感细胞BEL-7402和肝癌耐药细胞BEL-7402/5-FU作为实验对象,给予索拉菲尼、CⅡ-3和脱脂膏处理,检测自噬标志蛋白的生成,同时检测细胞中自噬相关因子和侵袭转移相关因子的水平以及细胞侵袭转移能力的变化。结果:耐药细胞组中p62蛋白低表达,给予阳性药索拉菲尼、CⅡ-3和脱脂膏后,细胞中p62蛋白表达量明显升高。和敏感细胞相比,耐药细胞中LC3B生成增多,给予CⅡ-3后LC3B生成减少。CⅡ-3和脱脂膏给药组均能明显抑制自噬和侵袭转移的部分相关因子的表达,包括降低ATG5、PIK3C3、BECLIN、LC3B、MMP-9、Akt、4EBP1mRNA表达。划痕试验结果显示,相比于敏感细胞,耐药细胞具有更强的侵袭转移能力,给予索拉菲尼和CⅡ-3作用后均可显著抑制细胞的侵袭转移,而脱脂膏则无显著的抑制效果。结论:肝癌耐药细胞具有很强的自噬和侵袭转移能力,而美洲大蠊提取物CⅡ-3和脱脂膏体外均能明显抑制耐药细胞的自噬和侵袭转移,但仅能影响部分相关因子。Objective:To investigate the effects of Periplaneta americana L.extract CⅡ-3 and the skimmed cream on the autophagy and metastatic invasion ability of 5-FU resistant hepatocellular carcinoma cells(Bel-7402/5-FU).Methods:Hepatocellular carcinoma-sensitive cells BEL-7402 and BEL-7402/5-FU were treated with sorafenib,CⅡ-3 and the skimmed cream to detect the production of autophagic marker proteins,as well as the levels of autophagy-related factors and invasion and metastasis-related factors in the cells and the changes in the invasion and metastasis ability of the cells.Results:P62 protein expression was low in the drug-resistant cell group,and the expression significantly increased after administration of positive drugs sorafenib,CⅡ-3 and the skimmed cream.Compared with sensitive cells,LC3B production increased in drug-resistant cells and decreased after administration of CⅡ-3.Both CⅡ-3 and the skimmed cream administration groups significantly inhibited the expression of some factors related to autophagy and invasive metastasis,including mRNA expression of ATG5,PIK3C3,BECLIN,LC3B,MMP-9,AKT,and 4EBP1.The results of scratch test showed that drug-resistant cells had stronger invasive metastasis ability compared with sensitive cells,and the administration of either sorafenib or CⅡ-3 significantly inhibited the invasive metastasis of the cells,while no significant inhibitory effect was observed for desiccated cream.Conclusion:Drug-resistant cells of hepatocellular carcinoma have strong autophagy and invasive metastasis ability,while both CⅡ-3 and skimmed cream of Periplaneta americana L.can significantly inhibit the autophagy and invasive metastasis of drug resistant cells in vitro,but can only affect some related factors.

关 键 词：美洲大蠊提取物 肝癌 自噬 侵袭转移 

分 类 号：R285[医药卫生—中药学]