Resveratrol abrogates the effects of hypoxia on cell proliferation, invasion and EMT in osteosarcoma cells through downregulation of the HIF-1α protein.
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.
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Yongming
Y
Sun
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Haibin
H
Wang
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Ming
M
Liu
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Fanguo
F
Lin
Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Jun
J
Hua
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013267:Stilbenes; D000077185:Resveratrol