1. Academic Validation
  2. Chemerin reverses the malignant phenotype and induces differentiation of human hepatoma SMMC7721 cells

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

  • Arch Pharm Res. 2021 Feb;44(2):194-204. doi: 10.1007/s12272-021-01311-z.
Ming Li  # 1 Pengcheng Sun  # 1 Kaikai Dong 1 Ye Xin 1 Aslee TaiLulu 1 Qinyu Li 2 Jing Sun 3 Min Peng 3 Ping Shi 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
  • 2 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China. drlqylqy@163.com.
  • 3 Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources, Northwest Institute of Plateau Biology, The Chinese Academy of Sciences, Xiguan Avenue 59, Xining, 810001, China.
  • 4 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China. ship@ecust.edu.cn.
  • 5 Qinghai Key Laboratory of Qinghai-Tibet Plateau Biological Resources, Northwest Institute of Plateau Biology, The Chinese Academy of Sciences, Xiguan Avenue 59, Xining, 810001, China. ship@ecust.edu.cn.
  • # Contributed equally.
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.

Keywords

Cell differentiation; Cell proliferation; Chemerin; Human hepatic carcinoma SMMC7721 cells; Malignant phenotype.

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