Chemerin reverses the malignant phenotype and induces differentiation of human hepatoma SMMC7721 cells.

Abstract	Chemerin exhibits an inhibitory effect on hepatocellular carcinoma; however, the underlying mechanism is unclear. Here, low chemerin expression was confirmed in samples of liver cancer patients and hepatoma cells. Chemerin altered hepatoma cell morphology but had no effect on normal hepatocytes. Chemerin inhibited proliferation of several human hepatoma cell lines. Real-time PCR detection of hepatocellular carcinoma markers showed that mRNA levels of albumin and A-type gamma-glutamyl transferase increased whereas those of alpha-fetoprotein, alkaline phosphatase, B-type gamma-glutamyl transferase, insulin-like growth factor II, and human telomerase reverse transcriptase decreased in chemerin-treated SMMC7721 cells. Western blotting revealed that chemerin up-regulated albumin and vimentin expressions, and downregulated alpha-fetoprotein expression. Phosphorylated STAT3 was significantly up-regulated, whereas phosphorylated ERK and AKT were significantly downregulated by chemerin. Chemerin decreased phosphorylated ERK and AKT expression and the cell proliferation induced by PI3K activator 740 Y-P but could not significantly alter phosphorylated STAT3 expression and the cell growth induced by STAT3 inhibitor NSC74859. In conclusion, chemerin reversed the malignant phenotype and induced SMMC7721 cell differentiation by inhibiting MAPK/ERK and PI3K/AKT signaling; growth inhibition by chemerin is not directly related to the JAK/STAT signaling pathway. Our study provides novel evidence that chemerin could be utilized for liver cancer treatment.
Authors	Ming Li, Pengcheng Sun, Kaikai Dong, Ye Xin, Aslee TaiLulu, Qinyu Li, Jing Sun, Min Peng, Ping Shi
Journal	Archives of pharmacal research (Arch Pharm Res) Vol. 44 Issue 2 Pg. 194-204 (Feb 2021) ISSN: 1976-3786 [Electronic] Korea (South)
PMID	33502677 (Publication Type: Journal Article)
Chemical References	Chemokines RARRES2 protein, human
Topics	Carcinoma, Hepatocellular (drug therapy, pathology) Cell Differentiation (drug effects, physiology) Cell Line, Transformed Cell Line, Tumor Chemokines (pharmacology, therapeutic use) Hep G2 Cells Humans Liver Neoplasms (drug therapy, pathology) Phenotype

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