Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines
10.16352/j.issn.1001-6325.2024.04.0440
- VernacularTitle: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
- Author:
Hongjiang GUO
1
;
Yeting XU
;
Diya ZHANG
;
Jiaxing QIU
;
Yucheng WANG
;
Rui JU
;
Lei GUO
Author Information
1. 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
- Keywords:
carboxyamidotriazole-orotate;
pancreatic cancer;
proliferation;
fatty acid anabolism
- From:
Basic & Clinical Medicine
2024;44(4):440-446
- CountryChina
- Language:Chinese
-
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.
