Pentamethylquercetin Inhibits Hepatocellular Carcinoma Progression and Adipocytes-induced PD-L1 Expression via IFN-γ Signaling

Author(s): Zhi Li, Wen-Qi Gao, Peng Wang, Tian-Qi Wang, Wen-Chao Xu, Xin-Yu Zhu, Hui Liu*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 11 , 2020


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Graphical Abstract:


Abstract:

Background: Obesity is a significant risk factor for the development of types of cancer. Programmed death 1 and its ligand programmed death-ligand 1 (PD-L1) play a crucial role in tumor immune escape. Although, the role of PD-L1 in obesity-associated hepatocellular carcinoma (HCC) remains unknown. We previously showed that the natural flavonoid pentamethylquercetin (PMQ) possesses anti-obesity properties.

Objective: This study was designed to investigate the effects of PMQ on the development of HCC in obese mice and whether PMQ regulates PD-L1 and expression in HCC.

Methods: Monosodium glutamate-induced obese mice were inoculated with H22 tumor cells. Tumor volumes and weights were measured. In vitro, 3T3-L1 preadipocytes were differentiated and lipid accumulation was measured by oil-red staining, and IFN-γ level was detected by Elisa. Hepatoma HepG2 cells were treated with conditional media from 3T3-L1 adipocytes (adi-CM). Western blotting was applied to detect PD-L1 protein levels in tumor tissue and HepG2 cells.

Results: Compared with control mice, H22 tumors grew faster and exhibited higher PD-L1 protein levels in obese mice. PMQ inhibited H22 tumor growth and reduced PD-L1 expression in tumor tissues. PD-L1 protein level was elevated in adi-CM-treated HepG2 cells. IFN-γ was detectable in adi-CM and exogenous IFN-γ induced PD-L1 expression in HepG2 cells. PMQ affected the differentiation of 3T3-L1 preadipocytes, decreased the level of IFN-γ secreted by adipocytes and downregulated adi-CM-induced PD-L1 expression in HepG2 cells.

Conclusion: PMQ could inhibit HCC progression in obese mice at least in part through down-regulating adipocytes-induced PD-L1 expression via IFN-γ signaling.

Keywords: Pentamethylquercetin, adipocytes, H22, HepG2, PD-L1, IFN-γ.

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VOLUME: 20
ISSUE: 11
Year: 2020
Page: [868 - 874]
Pages: 7
DOI: 10.2174/1568009620999200730184514
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