南方医科大学学报2025，Vol.45Issue(11)：2309-2319,11.DOI:10.12122/j.issn.1673-4254.2025.11.03
理冲消癥颗粒通过上调ANT3介导的线粒体凋亡增强小鼠卵巢癌移植瘤对顺铂的敏感性
Lichong Xiaozheng Granules enhances cisplatin sensitivity of ovarian cancer xenografts in rats by regulating adenine nucleotide translocator 3-mediated mitochondrial apoptosis
摘要
Abstract
Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.关键词
理冲消癥颗粒/腺苷酸转位酶3/线粒体凋亡/化疗增敏/卵巢癌Key words
Lichong Xiaozheng Granules/adenine nucleotide translocator 3/mitochondrial apoptosis/chemo-sensitization/ovarian cancer引用本文复制引用
陈一镠,马民,苏燃,朱寅宾,冯晴,罗嘉丽,冯伟峰,颜显欣..理冲消癥颗粒通过上调ANT3介导的线粒体凋亡增强小鼠卵巢癌移植瘤对顺铂的敏感性[J].南方医科大学学报,2025,45(11):2309-2319,11.基金项目
国家自然科学基金(82074430) （82074430）
广东省基础与应用基础研究基金项目(2024A1515011722) （2024A1515011722）
广州市科技计划项目(2024B03J1261,2024B03J1262) （2024B03J1261,2024B03J1262）
广东省中医药局科研项目(20241062) （20241062）
广东省基础与应用基础研究基金省企联合基金-面上项目(2022A1515220105) Supported by National Natural Science Foundation of China(82074430). （2022A1515220105）
