1. Academic Validation
  2. Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells

Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells

  • Pharmacol Res. 2020 May;155:104727. doi: 10.1016/j.phrs.2020.104727.
Zhe Wang 1 Ming Yue Li 1 Zhi Hong Zhang 1 Hong Xiang Zuo 1 Jing Ying Wang 1 Yue Xing 1 MyongHak Ri 1 Hong Lan Jin 1 Cheng Hua Jin 1 Guang Hua Xu 1 Lian Xun Piao 1 Chang Gao Jiang 2 Juan Ma 3 Xuejun Jin 4
Affiliations

Affiliations

  • 1 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.
  • 2 Department of Gastroenterology, Affiliated Hospital of Yanbian University, Yanji, 133000, Jilin Province, China. Electronic address: [email protected].
  • 3 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China. Electronic address: [email protected].
  • 4 Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China. Electronic address: [email protected].
Abstract

Panaxadiol is a triterpenoid sapogenin monomeric compound found in the roots of Panax ginseng and has a variety of biological activities such as neuroprotective and anti-tumour functions. However, the mechanisms how panaxadiol exerts the Anticancer effects remain unknown. The current study aimed to investigate the potential activity of panaxadiol on programmed cell death-ligand 1 (PD-L1) expression and tumour proliferation in human colon Cancer cells and to identify the underlying mechanism. Results showed that panaxadiol showed little cytotoxicity as assessed by a cytotoxicity assay and significantly inhibited PD-L1 expression at the protein and mRNA level in a dose-dependent manner. Furthermore, panaxadiol supressed the hypoxia-induced synthesis of hypoxia-inducible factor (HIF)-1α via the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways without affecting HIF-1α degradation. Simultaneously, panaxadiol inhibited STAT3 activation through the JAK1, JAK2, and Src pathways. Moreover, pre-treatment with panaxadiol enhanced the activity of cytotoxic T lymphocytes (CTL) and regained their capacity of tumour cell killing in a T cell and tumour cell co-culture system. Immunoprecipitation showed that panaxadiol inhibited PD-L1 expression by blocking the interaction between HIF-1α and STAT3. The inhibitory effect of panaxadiol on tumour proliferation was further demonstrated by colony formation and EdU labelling assays. The anti-proliferative effect of panaxadiol was also proved by a xenograft assay in vivo. Taken together, the current work highlights the anti-tumour effect of panaxadiol, providing insights into development of Cancer therapeutic through PD-L1 inhibition.

Keywords

Cancer immunotherapy; Nature product; PD-L1 inhibitor; Panax ginseng; T cells.

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