Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells

  • Authors:
    • Ri-Xiong Wang
    • Hui Liu
    • Li Xu
    • Hui Zhang
    • Rui-Xiang Zhou
  • View Affiliations

  • Published online on: September 1, 2015     https://doi.org/10.3892/or.2015.4238
  • Pages: 2541-2546
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Abstract

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 conce­ntration-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.
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November-2015
Volume 34 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wang R, Liu H, Xu L, Zhang H and Zhou R: Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells. Oncol Rep 34: 2541-2546, 2015.
APA
Wang, R., Liu, H., Xu, L., Zhang, H., & Zhou, R. (2015). Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells. Oncology Reports, 34, 2541-2546. https://doi.org/10.3892/or.2015.4238
MLA
Wang, R., Liu, H., Xu, L., Zhang, H., Zhou, R."Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells". Oncology Reports 34.5 (2015): 2541-2546.
Chicago
Wang, R., Liu, H., Xu, L., Zhang, H., Zhou, R."Involvement of nuclear receptor RZR/RORγ in melatonin-induced HIF-1α inactivation in SGC-7901 human gastric cancer cells". Oncology Reports 34, no. 5 (2015): 2541-2546. https://doi.org/10.3892/or.2015.4238