Thyroxine inhibits resveratrol-caused apoptosis by PD-L1 in ovarian cancer cells.

Autor:	Chin YT; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan., Wei PL; Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.; Cancer Research Center and Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.; Department of Surgery, College of Medicine; Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan., Ho Y; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan., Nana AW; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan., Changou CA; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.; Core Facility, Taipei Medical University, Taipei, Taiwan.; Integrated Laboratory, Center of Translational Medicine, Taipei Medical University, Taipei, Taiwan., Chen YR; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan., Yang YS; Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan., Hsieh MT; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan., Hercbergs A; Department of Radiation Oncology, The Cleveland Clinic, Cleveland, Ohio, USA., Davis PJ; Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.; Department of Medicine, Albany Medical College, Albany, New York, USA., Shih YJ; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan., Lin HY; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.; Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.; Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Endocrine-related cancer [Endocr Relat Cancer] 2018 May; Vol. 25 (5), pp. 533-545. Date of Electronic Publication: 2018 Mar 19.
DOI:	10.1530/ERC-17-0376
Abstrakt:	Thyroid hormone, l-thyroxine (T 4 ), has been shown to promote ovarian cancer cell proliferation via a receptor on plasma membrane integrin αvβ3 and to induce the activation of ERK1/2 and expression of programmed death-ligand 1 (PD-L1) in cancer cells. In contrast, resveratrol binds to integrin αvβ3 at a discrete site and induces p53-dependent antiproliferation in malignant neoplastic cells. The mechanism of resveratrol action requires nuclear accumulation of inducible cyclooxygenase (COX)-2 and its complexation with phosphorylated ERK1/2. In this study, we examined the mechanism by which T 4 impairs resveratrol-induced antiproliferation in human ovarian cancer cells and found that T 4 inhibited resveratrol-induced nuclear accumulation of COX-2. Furthermore, T 4 increased expression and cytoplasmic accumulation of PD-L1, which in turn acted to retain inducible COX-2 in the cytoplasm. Knockdown of PD-L1 by small hairpin RNA (shRNA) relieved the inhibitory effect of T 4 on resveratrol-induced nuclear accumulation of COX-2- and COX-2/p53-dependent gene expression. Thus, T 4 inhibits COX-2-dependent apoptosis in ovarian cancer cells by retaining inducible COX-2 with PD-L1 in the cytoplasm. These findings provide new insights into the antagonizing effect of T 4 on resveratrol's anticancer properties. (© 2018 Society for Endocrinology.)
Databáze:	MEDLINE
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