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.