27-Hydroxycholesterol modulates lung cancer cell proliferation by activation of LXR signaling pathway
10.3969/j.issn.1000-4718.2019.02.013
- VernacularTitle:27-羟基胆固醇激活LXR信号通路调节肺癌细胞的增殖
- Author:
You-Yun FU
1
;
Ting CHEN
;
Xiao-Jing LIN
;
Jing GAO
;
Xue-Mei LIAN
Author Information
1. 重庆医科大学脂糖代谢性疾病重庆市重点实验室感染性疾病分子生物学教育部重点实验室
- Keywords:
27-Hydroxycholesterol;
LXR signaling pathway;
Cell proliferation;
Lung cancer
- From:
Chinese Journal of Pathophysiology
2019;35(2):267-272
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of cholesterol metabolite 27-hydroxycholesterol (27-OHC) on the proliferation of lung cancer cells.METHODS:Human lung cancer A549 cells were treated with 27-OHC at different concentrations (0, 0.3125, 0.625, 1.25, 2.5, 5 and 10μmol/L) for 24～48 h.The cell viability, cell cycle, cell proliferation, the intracellular cholesterol levels and cholesterol metabolism-related molecule expression were subsequently assessed by CCK-8 assay, flow cytometry, Ed U staining, tissue total cholesterol detection kit, real-time PCR and Western blot.RESULTS:27-OHC decreased the viability of the A549 cells in a dose-and time-dependent manner (P<0.01) and inhibited the cell proliferation (P<0.05).The expression of typical liver X receptor (LXR) downstream target proteins including ATP-binding cassette transporter A1 (ABCA1) , low-density lipoprotein receptor (LDLR) , and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CR) were modulated, which promoted the efflux of intracellular cholesterol, and reduced cholesterol influx and de novo synthesis, resulting in decreased intracellular cholesterol levels and cell viability.Furthermore, the inhibitory effect of 27-OHC on A549 cell viability was significantly attenuated after the LXR pathway was partially blocked by 5μmol/L GSK2033 treatment (P<0.05).CONCLUSION:27-OHC inhibits A549 cell proliferation via activation of LXR signaling pathway.
