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Cholesterol attenuated the progression of DEN-induced hepatocellular carcinoma via inhibiting SCAP mediated fatty acid de novo synthesis.

Abstract：

:Worldwide, hepatocellular carcinoma (HCC) remains a top instigator of cancer mortality. Previous clinical studies have revealed that low serum cholesterol predicts a poor outcome in HCC patients, but the potential role of cholesterol in the progression of HCC remains controversial. In the present study,we tested the influence of cholesterol on the progression of DEN-induced HCC by feeding mice with a high cholesterol diet (HCD) and by depriving cholesterol with atorvastatin, a widely used inhibitor of the mevalonate pathway. We found that HCD induced more and larger liver tumors and an increased occurrence of lung metastasis in DEN-injected mice. These effects could be prevented by cholesterol deprivation with atorvastatin. In vitro, cholesterol loading repressed the proliferation, migration, and the invasion of SK hep1 cells, which was additionally prevented by cholesterol deprivation. Both in vivo and in vitro, cholesterol loading decreased the expression of Sterol regulatory element-binding protein cleavage-activating protein (SCAP), the translocation of sterol regulatory element-binding protein1 (SREBP1) to the nucleolus, and the genetic expression of FAS and ACC-1. Over-expression of SCAP in cholesterol-loaded SK hep1 cells promoted the nuclear translocation of SREBP1 and the expression of FAS and ACC-1, which promoted the proliferation, migration, and the invasion of SK hep1 cells. Knockdown of SCAP also restrained the cholesterol deletion-mediated up-regulation of fatty acid de novo synthesis in SK hep1 cells, inhibiting the atorvastatin-mediated proliferation, migration, and invasion of SK hep1 cells. In conclusion, cholesterol inhibited the progression of HCC through restraining SCAP-mediated fatty acid de novo synthesis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhao Z,Zhong L,He K,Qiu C,Li Z,Zhao L,Gong J

doi

10.1016/j.bbrc.2018.12.181

subject

Has Abstract

pub_date

2019-02-19 00:00:00

pages

855-861

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)32868-7

journal_volume

509

pub_type

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Cholesterol attenuated the progression of DEN-induced hepatocellular carcinoma via inhibiting SCAP mediated fatty acid de novo synthesis.