Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways


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Background:Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named Schisandra rubriflora (Franch.).

Purpose:In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 in vitro and in vivo.

Materials and Methods:In vitro, we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. In vivo, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

Results:We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 via JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, in vivo observation confirmed the antitumor activity of schisanhenol.

Conclusion:Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 via the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.

Об авторах

Zhihong Zhang

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Yiwen Zhong

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Xu Han

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Xueyang Hu

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Yuhan Wang

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Lei Huang

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Siying Li

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Ziqing Li

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Chunmei Wang

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

He Li

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Jinghui Sun

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Wenyue Zhuang

Department of Molecular Biology Test Technique, College of Medical Technology, Beihua University

Email: info@benthamscience.net

Mengyang Wang

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Jianguang Chen

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Wei Liu

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Chang Liu

Department of Pharmacology, College of Pharmacy, Beihua University

Email: info@benthamscience.net

Xin Guo

School of Pharmacy and Medicine, Tonghua Normal University

Email: info@benthamscience.net

Siyu Yuan

Department of Pharmacy, Siping Central People's Hospital

Email: info@benthamscience.net

Jiping Wu

Department of Immunology, School of Basic Medicine, Beihua University

Автор, ответственный за переписку.
Email: info@benthamscience.net

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