Resveratrol antagonizes thyroid hormone-induced expression of checkpoint and proliferative genes in oral cancer cells

Chia Cheng Lin, Yu Tang Chin, Ya Jung Shih, Yi Ru Chen, Yao Yu Chung, Chi Yu Lin, Chao Nan Hsiung, Jacqueline Whang-Peng, Sheng Yang Lee, Hung Yun Lin, Paul J. Davis, Kuan Wang

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11 引文 斯高帕斯(Scopus)

摘要

Background/purpose: Dysregulation of cell cycle checkpoint control may lead to the independence of growth regulating signals. Checkpoint protein such as the PD-1/PD-L1 immune checkpoint involving tumor cells and host immune defense lymphocytes is a well-studied therapeutic target in oncology. Acting at a cell surface receptor on plasma membrane integrin αvβ3, thyroxine stimulates intracellular accumulation of PD-L1 in cancer cells. Although resveratrol also binds to integrin αvβ3, it reduces PD-L1 expression. Materials and methods: In current studies, we investigated the roles of resveratrol and thyroxine in regulating expression of proliferation-related genes and checkpoint genes, PD-L1, BTLA in two oral cancer cell lines. Results: Thyroxine suppressed the expression of pro-apoptotic BAD but induced proliferative CCND1 expression in SSC-25 cells and OEC-M1 cells. It activated expression of PD-L1 and BTLA in both cell lines. On the other hand, resveratrol suppressed the expression of all. Alternatively, it activated BAD expression. Thus thyroxine induces checkpoint gene expression which may promote proliferation in cancer cells. Alternatively, resveratrol reverses the stimulatory effects of thyroid hormone to induce anti-proliferation. Conclusion: These findings provide new insights into the antagonizing effect of resveratrol on the thyroxine-induced expression of checkpoint genes and proliferative genes in oral cancers.
原文英語
頁(從 - 到)255-262
頁數8
期刊Journal of Dental Sciences
14
發行號3
DOIs
出版狀態已發佈 - 九月 1 2019

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