2. Academic Validation
  3. Upregulation of 24(R/S),25-epoxycholesterol and 27-hydroxycholesterol suppresses the proliferation and migration of gastric cancer cells

Upregulation of 24(R/S),25-epoxycholesterol and 27-hydroxycholesterol suppresses the proliferation and migration of gastric cancer cells

  • Biochem Biophys Res Commun. 2018 Oct 12;504(4):892-898. doi: 10.1016/j.bbrc.2018.09.058.
Fenghua Guo 1,  Wenting Hong 2,  Mingjie Yang 2,  Dongke Xu 2,  Qianming Bai 3,  Xiaobo Li 4,  Zongyou Chen 5
Affiliations

Affiliations

  • 1 Department of General Surgery, Hua'shan Hospital, Fudan University Shanghai Medical College, Shanghai, China.
  • 2 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 3 Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • 4 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China. Electronic address: xbli@fudan.edu.cn.
  • 5 Department of General Surgery, Hua'shan Hospital, Fudan University Shanghai Medical College, Shanghai, China. Electronic address: zongyouchen@hotmail.com.
PMID: 30224060 DOI: 10.1016/j.bbrc.2018.09.058
Abstract

Gastric Cancer (GC) is one of the most common cancers and is the second-leading cause of cancer-associated morbidity worldwide. Oxysterols are oxidized derivatives of Cholesterol that may be important in many biological processes, but the levels and roles of oxysterols in gastric tumours remain to be elucidated. The levels of Cholesterol, oxysterols and sulfated oxysterols in human gastric tumour tissues, adjacent normal mucosal tissues, cancerous gastric juice and gastric juice obtained from healthy subjects were detected by LC-MS. It was found that the levels of 24(R/S),25-EC and 27HC in human gastric tumour tissues and cancerous gastric juice were significantly increased compared with those of adjacent normal mucosal tissues and gastric juice from healthy subjects. Compared with normal gastric mucosal tissue, the levels of sulfated 25-hydroxycholesterol (25HC3S) and the ratio of 25HC3S/25HC were decreased in human gastric tumour tissues, which might be related to the dramatically decreased SULT2A1 expression in gastric tumour tissue. Both 24(R/S),25-EC and 27HC suppressed gastric Cancer proliferation, which was not altered by LXRα-siRNA treatment. The suppression of cell proliferation induced by 27HC was attenuated by LXRβ-siRNA, but the suppression of cell proliferation induced by 24(R/S),25-EC was intensified by LXRβ-siRNA. Both 24(R/S),25-EC and 27HC dramatically inhibited HGC-27 cell migration, which was attenuated by the co-transfection of cells with LXRα-siRNA and LXRβ-siRNA, but not LXRα-siRNA or LXRβ-siRNA alone. In conclusion, the accumulated 24(R/S),25-EC and 27HC in human gastric tumour tissues might play important roles in gastric Cancer development.

Keywords

24(R/S),25-epoxycholesterol; 27-Hydroxycholesterol; Gastric cancer; Oxysterols.

Figures
Products