艾迪注射液抗HepG2裸鼠移植瘤的作用及对胆碱代谢通路的影响  

Anti-tumor effect of Aidi injection on HepG2 transplanted tumor in nude mice and its effect on choline metabolism pathway

作　　者：费炳红[1] 于东升 郭丹风 李晓萍[1] FEI Binghong;YU Dongsheng;GUO Danfeng;LI Xiaoping(Department of Chinese Medicine,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052;Henan Key Laboratory for Digestive Organ Transplantation,Zhengzhou 450052)

机构地区：[1]郑州大学第一附属医院中药科,郑州4500522 [2]河南省消化器官移植重点实验室,郑州450052

出　　处：《郑州大学学报(医学版)》2025年第2期149-153,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金青年基金项目(81900468,81901571);河南省重点研发与推广专项(222102310534);河南省慈善联合总会肝胆相照基金项目(GDXZ2023022)。

摘　　要：目的:探讨艾迪注射液(ADI)抗肝细胞癌(HCC)HepG2裸鼠移植瘤的作用及对胆碱代谢通路的影响。方法:将1×10^(6)个/mL的HepG2细胞按0.1 mL/只接种于裸鼠右腋下,待移植瘤体积达到50 mm^(3)时,将裸鼠随机分为2组,每组6只,分别腹腔注射20 mL/kg生理盐水(模型组)或20 mL/kg ADI(ADI组),隔天1次。给药8次后,处死小鼠,测量肿瘤体积;收集血清进行非靶向代谢组学检测,筛选出与癌症胆碱代谢通路有关的差异代谢物;Western blot和RT-qPCR法检测肿瘤组织中CHKα的表达水平。结果:ADI组肿瘤体积小于模型组(P<0.05);血清代谢组学分析显示,两组代谢物轮廓差异较大,在癌症中胆碱代谢通路中富集到2个差异代谢物,1,2-二棕榈酰-sn-甘油-3-磷酰胆碱(DPPC)和1-硬脂酰基-2-花生四烯酸-sn-甘油(1,2-SAG),ADI组两者血清水平均低于模型组(P<0.05)。ADI组肿瘤组织中CHKα蛋白和mRNA表达水平均低于模型组(P<0.05)。结论:ADI通过下调CHKα表达,抑制肿瘤细胞胆碱代谢,从而发挥抑制HCC进展的作用。Aim:To investigate the anti-tumor effect of Aidi injection(ADI)on hepatocellular carcinoma(HCC)HepG2 transplanted tumor in nude mice and its effect on choline metabolism pathway.Methods:HepG2 cells(1×10^(6)cells/mL)were inoculated at 0.1 mL per mouse into the right axilla of nude mice.When the volume of the transplanted tumors reached 50 mm^(3),the nude mice were randomly allocated into 2 groups,with 6 mice in each group:one group received intraperitoneal injections of 20 mL/kg normal saline(model group),and the other group received 20 mL/kg ADI(ADI group),and the injections were administered every other day.After 8 administrations,the mice were euthanized,and the tumor volumes were measured.Serum was collected for untargeted metabolomics analysis to identify differential metabolites associated with the cancer choline metabolism pathway.The protein and mRNA expression levels of CHKαin tumor tissue were detected by Western blot and RT-qPCR.Results:The tumor volume in the ADI group was significantly smaller than that in the model group(P<0.05).Serum metabolomics analysis revealed significant differences in metabolite profiles between the 2 groups,with 2 differential metabolites enriched in the cancer choline metabolism pathway:1,2-dihexadecanoyl-sn-glycero-3-phosphocholine(DPPC)and 1-stearoyl-2-arachidonoyl-sn-glycerol(1,2-SAG).The expression levels of both metabolites were lower in the ADI group compared with the model group(P<0.05).Additionally,the protein and mRNA expression levels of CHKαin tumor tissue in the ADI group were significantly lower than those in the model group(P<0.05).Conclusion:ADI exerts its inhibitory effect on the progression of HCC by downregulating the expression of CHKα,thereby suppressing choline metabolism in tumor cells.

关 键 词：肝细胞癌 艾迪注射液 胆碱激酶A 非靶代谢组学 裸鼠 

分 类 号：R735.7[医药卫生—肿瘤]