天然产物研究与开发2026，Vol.38Issue(8)：1652-1660,1734,10.DOI:10.16333/j.1001-6880.2026.8.003
基于BNIP3/BNIP3L信号通路的芹菜素诱导结直肠癌线粒体自噬的机制研究
Mechanism of apigenin-induced mitophagy in colorectal cancer based on BNIP3/BNIP3L signaling pathway
摘要
Abstract
The study aims to investigate the effect of apigenin on the mitophagy in colorectal cancer cells and its underlying mechanism based on the B-cell lymphoma 2(BCL-2)/adenovirus E1B 19 kDa protein-interacting protein 3(BNIP3)/BCL-2/adenovirus E1B 19 kDa protein-interacting protein 3-like(BNIP3L)signaling pathway.The effect of apigenin on the prolif-eration of human colorectal cancer LoVo cells was detected by MTT assay.The efficacy of apigenin on the clonality of LoVo cells was examined by colony formation assay.The influence of apigenin on the morphology of the mitophagy in LoVo cells was observed by transmission electron microscopy.The impact of apigenin on the ATP content in LoVo cells was assessed by the ATP kit.The potency of apigenin on the mitochondrial membrane potential was evaluated by the JC-1 kit.The RT-qPCR was performed to analyze the effect of apigenin on the mitophagy-related mRNA expressions in LoVo cells.The Western blot anal-ysis was conducted to probe the influence of apigenin on the mitophagy-related protein levels in LoVo cells.Compared with the control,apigenin significantly inhibited the proliferation and colony formation of LoVo cells,and induced the morphological features of mitophagy in LoVo cells.Meanwhile,apigenin decreased the ATP content and mitochondrial membrane potential of LoVo cells,which was synergized by the activator of mitophagy named CCCP,and antagonized by the inhibitor of mitophagy named Mdivi-1.Additionally,apigenin significantly increased the mRNA and protein expression levels of microtubule-associat-ed protein 1A/1B-light chain 3(LC3),BNIP3 and BNIP3L in LoVo cells(P＜0.05 or P＜0.01),but mitigated the mRNA and protein expression levels of P62(sequestosome 1,SQSTM1),the translocase of the inner mitochondrial membrane 23 kDa subunit(TIMM23)and the translocase of the outer mitochondrial membrane 20 kDa subunit(TOMM20)in LoVo cells(P＜0.05 or P＜0.01).Taken together,apigenin can induce the mitophagy of colorectal cancer by heightening the activity of the BNIP3/BNIP3L signaling pathway,so as to exert the anti-colorectal cancer effect.关键词
芹菜素/结直肠癌/线粒体自噬/BNIP3/BNIP3L/LoVo细胞Key words
apigenin/colorectal cancer/mitophagy/BNIP3/BNIP3L/LoVo cells分类
医药卫生引用本文复制引用
何紫雨,唐晓梦,刘晓虹,罗文雯,胡佳豪,明天琪,李煜兵,徐海波..基于BNIP3/BNIP3L信号通路的芹菜素诱导结直肠癌线粒体自噬的机制研究[J].天然产物研究与开发,2026,38(8):1652-1660,1734,10.基金项目
国家自然科学基金(81573813) （81573813）
四川省自然科学基金面上项目(2023NSFSC0653) （2023NSFSC0653）
