基础医学与临床2024，Vol.44Issue(4)：440-446,7.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
Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines
摘要
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 sulfo-nylrhodamine 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 de-creased 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.关键词
羧胺三唑乳清酸盐/胰腺癌/增殖/脂肪酸合成代谢Key words
carboxyamidotriazole-orotate/pancreatic cancer/proliferation/fatty acid anabolism分类
医药卫生引用本文复制引用
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):440-446,7.基金项目
国家自然科学基金(82002094) （82002094）
中国医学科学院医学与健康科技创新工程(2022-I2M-2-002) （2022-I2M-2-002）
北京市自然科学基金(7222254) （7222254）
