羧胺三唑乳清酸盐对人胰腺癌细胞系增殖及脂肪酸合成代谢的影响

doi:10.16352/j.issn.1001-6325.2024.04.0440

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (4): 440-446.doi: 10.16352/j.issn.1001-6325.2024.04.0440

羧胺三唑乳清酸盐对人胰腺癌细胞系增殖及脂肪酸合成代谢的影响

郭泓江, 徐也婷, 张迪雅, 仇佳星, 王钰铖, 鞠瑞^*, 郭磊^*

中国医学科学院基础医学研究所北京协和医学院基础学院药理学系,北京 100005

收稿日期:2023-12-01 修回日期:2024-01-23 出版日期:2024-04-05 发布日期:2024-03-25
通讯作者: ^*jurui1984@163.com;leiguo@ibms.cams.cn
基金资助:
国家自然科学基金(82002094);中国医学科学院医学与健康科技创新工程(2022-I2M-2-002);北京市自然科学基金(7222254)

Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines

GUO Hongjiang, XU Yeting, ZHANG Diya, QIU Jiaxing, WANG Yucheng, JU Rui^*, GUO Lei^*

Department of Pharmacology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005,China

Received:2023-12-01 Revised:2024-01-23 Online:2024-04-05 Published:2024-03-25
Contact: ^*jurui1984@163.com;leiguo@ibms.cams.cn

摘要/Abstract

摘要： 目的研究羧胺三唑乳清酸盐(CTO)对人胰腺癌细胞增殖影响及对其脂肪酸合成代谢的调控作用。方法以人胰腺癌细胞系AsPC-1、AsPC-1/GEM(简称AR)、PANC-1、MiaPaCa-2为研究对象,用磺酰罗丹明B(SRB)检测细胞存活率,采用qPCR检测胰腺癌细胞系中脂肪酸合成关键基因mRNA水平,用Western blot检测细胞内腺苷单磷酸依赖蛋白激酶(AMPK)和乙酰辅酶A羧化酶(ACC)通路蛋白表达;利用液相色谱-质谱联用代谢组学技术检测细胞内脂质代谢物质差异。结果与对照组相比,CTO显著降低AsPC-1、AR、PANC-1、MiaPaCa-2 4株人胰腺癌细胞活率(P＜0.05); CTO下调细胞内脂肪酸合成关键基因的mRNA水平(P＜0.05);CTO下调细胞中AMPK、ACC及c-Myc蛋白表达(P＜0.05),而增加p-AMPK、p-ACC蛋白表达(P＜0.05);CTO减少AR细胞中脂质代谢物含量(P＜0.05)。结论 CTO通过抑制癌基因c-Myc蛋白表达及AMPK/ACC通路,下调脂肪酸合成相关基因的表达活性,减弱细胞脂肪酸合成代谢能力,进而抑制人胰腺癌细胞系AsPC-1、AR、PANC-1、MiaPaCa-2的增殖能力。

关键词: 羧胺三唑乳清酸盐, 胰腺癌, 增殖, 脂肪酸合成代谢

Abstract: Objective To study the effect of carboxyamidotriazole-orotate(CTO) on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells. Methods Human pancreatic cancer cell lines AsPC-1, AsPC-1/GEM(AR), PANC-1 and MiaPaCa-2 were used as the study subjects; cell survival rate was detected by sulfonylrhodamine B(SRB); the mRNA level of key genes for fatty acid synthesis was detected by qPCR; the protein level of the AMPK/ACC pathway was detected by Western blot; intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS). Results Comparing to control group, CTO significantly decreased the cell viability of AsPC-1, AR, PANC-1, and MiaPaCa-2(P＜0.05). CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05). CTO significantly reduced the protein expression of AMPK, ACC and c-Myc(P＜0.05), while increasing the protein expression of p-AMPK and p-ACC(P＜0.05). CTO decreased lipid metabolite content in AR cells(P＜0.05). Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway, down-regulates the expression of fatty acid synthesis-related genes, and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1, AR, PANC-1 and MiaPaCa-2.

Key words: carboxyamidotriazole-orotate, pancreatic cancer, proliferation, fatty acid anabolism

中图分类号:

郭泓江, 徐也婷, 张迪雅, 仇佳星, 王钰铖, 鞠瑞, 郭磊. 羧胺三唑乳清酸盐对人胰腺癌细胞系增殖及脂肪酸合成代谢的影响[J]. 基础医学与临床, 2024, 44(4): 440-446.

GUO Hongjiang, XU Yeting, ZHANG Diya, QIU Jiaxing, WANG Yucheng, JU Rui, GUO Lei. Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines[J]. Basic & Clinical Medicine, 2024, 44(4): 440-446.

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羧胺三唑乳清酸盐对人胰腺癌细胞系增殖及脂肪酸合成代谢的影响

Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines

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