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

[ Vol. 20 , Issue. 11 ]

Author(s):

Zhi Li, Wen-Qi Gao, Peng Wang, Tian-Qi Wang, Wen-Chao Xu, Xin-Yu Zhu and Hui Liu*Pages 868-874 (7)

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.

Affiliation:

Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan

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