Cobalt chloride inhibits tumor formation in osteosarcoma cells through upregulation of HIF-1α

The exact effect of hypoxia on cancer development is controversial. The present study investigates the ability of osteosarcoma to form tumors in the hypoxic microenvironment induced by CoCl(2). MG63 human osteosarcoma cells were cultured with different concentrations (0, 150 and 300 μM) of CoCl(2) for 24 h to simulate hypoxia in vitro. The expression of hypoxia-inducible factor (HIF)-1α was analyzed by western blotting. The proliferation and drug resistance of MG63 cells were examined using the CCK-8 assay, the apoptosis rate was detected by flow cytometry, the ability to form spheroids was assessed by a sarcosphere culture system and invasiveness was determined by a vertical invasion assay. A transplantation assay was used to evaluate the ability to form tumors in vivo. Our results showed that the proliferation of MG63 cells was inhibited by treatment with CoCl(2), while no effect on drug toxicity was observed. The apoptotic rate was increased in a dose-dependent manner, the ability to form sarcospheroids was suppressed, the invasiveness was inhibited and the expression of HIF-1α was upregulated following CoCl(2) treatment. We also found that the ability to form tumors in vivo was inhibited. In conclusion, we provide strong evidence that CoCl(2) has the ability to inhibit osteosarcoma development; the mechanism may be related to the hypoxic microenvironment and HIF-1α may be a critical regulatory factor.