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Pentamethylquercetin Inhibits Hepatocellular Carcinoma Progression and Adipocytes-induced PD-L1 Expression via IFN-γ Signaling.
- Source :
-
Current cancer drug targets [Curr Cancer Drug Targets] 2020; Vol. 20 (11), pp. 868-874. - Publication Year :
- 2020
-
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.<br />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.<br />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.<br />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.<br />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.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- 3T3-L1 Cells
Adipocytes drug effects
Adipocytes metabolism
Animals
Cell Differentiation drug effects
Cell Proliferation drug effects
Flavonoids chemistry
Flavonoids pharmacology
Hep G2 Cells
Humans
Lipid Metabolism drug effects
Mice
Mice, Obese
Plant Extracts
Signal Transduction drug effects
Treatment Outcome
B7-H1 Antigen metabolism
Carcinoma, Hepatocellular drug therapy
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Interferon-gamma metabolism
Liver Neoplasms drug therapy
Liver Neoplasms metabolism
Liver Neoplasms pathology
Obesity metabolism
Quercetin chemistry
Quercetin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5576
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Current cancer drug targets
- Publication Type :
- Academic Journal
- Accession number :
- 32748749
- Full Text :
- https://doi.org/10.2174/1568009620999200730184514