Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells
Autor: | Rui-Xiang Zhou, Li Xu, Hui Zhang, Hui Liu, Ri-Xiong Wang |
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Rok vydání: | 2015 |
Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research medicine.medical_specialty Cell Survival Cell Gene Expression Biology Melatonin chemistry.chemical_compound Stomach Neoplasms Cell Line Tumor Internal medicine Endopeptidases medicine Humans Cell Proliferation Cell growth General Medicine Nuclear Receptor Subfamily 1 Group F Member 3 Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Gene Expression Regulation Neoplastic Vascular endothelial growth factor Cysteine Endopeptidases Endocrinology medicine.anatomical_structure Oncology chemistry Nuclear receptor Apoptosis Cancer cell Cancer research Signal transduction hormones hormone substitutes and hormone antagonists Signal Transduction medicine.drug |
Zdroj: | Oncology Reports. 34:2541-2546 |
ISSN: | 1791-2431 1021-335X |
Popis: | The melatonin nuclear receptor is an orphan member of the nuclear receptor superfamily RZR/ROR, which consists of three subtypes (α, β and γ), suggesting that immunomodulatory and antitumor effects through the intracellular action of melatonin depend on nuclear signaling. In the present study, the biological mechanisms of melatonin were elucidated in association with the RZR/RORγ pathway in SGC-7901 human gastric cancer cells under hypoxia. Melatonin suppressed the activity of RZR/RORγ and SUMO-specific protease 1 (SENP1) signaling pathway, which is essential for stabilization of hypoxia‑inducible factor-1α (HIF‑1α) during hypoxia. Furthermore, melatonin inhibited the stability of HIF-1α in a time- and conce-ntration-dependent manner in SGC-7901 human gastric cancer cells during hypoxia. Consistently, siRNA-RZR/RORγ effectively blocked the expression of SENP1, HIF-1α and vascular endothelial growth factor (VEGF) production in SGC-7901 cells under hypoxia, suggesting the role of nuclear receptor RZR/RORγ in melatonin-inhibited HIF-1α and VEGF accumulation. Moreover, siRNA RZR/RORγ obviously antagonized to inhibit the action of the gastric cancer cell proliferation by melatonin. Our findings suggest that melatonin suppresses HIF-1α accumulation and VEGF generation via inhibition of melatonin nuclear receptor RZR/RORγ in SGC-7901 cells under hypoxia. |
Databáze: | OpenAIRE |
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