Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1α protein

Sun,Yongming; Wang,Haibin; Liu,Ming; Lin,Fanguo; Hua,Jun

doi:10.3892/mmr.2014.2913

Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1α protein

Authors:
- Yongming Sun
- Haibin Wang
- Ming Liu
- Fanguo Lin
- Jun Hua
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Affiliations: Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
Published online on: November 10, 2014 https://doi.org/10.3892/mmr.2014.2913
Pages: 1975-1981

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Abstract

Resveratrol has been shown to have antineoplastic effects in vivo and in vitro. However, the effect of resveratrol on the hypoxia-enhanced proliferation and invasion of osteosarcoma cells remains unclear. In this study, we investigated the role of resveratrol on regulating proliferation and invasion of osteosarcoma cells under hypoxic conditions. Saos-2 cells were cultured under controlled hypoxic conditions (3% O2) or normoxic conditions. Resveratrol (50 µM) was added in the medium, and hypoxia inducible factor-1α (HIF-1α) siRNA was used to inhibit HIF-1α transcription. Proliferation of Saos-2 cells was evaluated by the methabenzthiazuron (MTT) assay. The invasive ability of Saos-2 cells was determined by a Transwell assay. HIF-1α, E-cadherin and vimentin protein levels were detected by western blot analysis. HIF-1α, E-cadherin and vimentin mRNA levels were assessed by RT-PCR. Compared to the control group, hypoxia significantly increased the proliferation rate and invasive ability of Saos-2 cells. Moreover, hypoxia markedly increased the E-cadherin level and decreased vimentin expression. However, resveratrol or HIF-1α silencing reverted all the above effects of hypoxia in Saos-2 cells. Moreover, resveratrol inhibited HIF-1α protein accumulation without affecting the HIF-1α mRNA level. These data suggest that resveratrol can inhibit the hypoxia‑enhanced proliferation, invasion and epithelial to mesenchymal transition process in osteosarcoma via downregulation of the HIF-1α protein. Thus, HIF-1α may be a promising drug target of resveratrol in the context of development of anticancer therapy for human osteosarcoma.

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