The effect of histone deacetylase inhibitor on invasion and expression of HIF-1 α in osteosarcoma
10.3781/j.issn.1000-7431.2008.06.004
- Author:
Qing-Cheng YANG
1
Author Information
1. Department of Orthopaedics
- Publication Type:Journal Article
- Keywords:
Alpha subunit;
Hypoxia-inducible factor 1;
Neoplasm invasiveness;
Osteosarcoma;
Trichostatin A
- From:
Tumor
2008;28(6):472-475
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the anticancer activity of histone deacetylase (HDAC) inhibitor trichostatin A (TSA) on osteosarcoma in vitro and its possible mechanism. Methods: Osteosarcoma MG-63 cells were cultured under the mimic hypoxia condition induced by desferrioxamine and treated with TSA in vitro. The effects of TSA on invasion of MG-63 cells was detected by Transwell migration assay. The effect of TSA on mRNA and protein expressions of HIF-1α and VEGF were tested by RT-PCR, Western blotting, and ELISA at various concentrations and different time points. Results: After treatment with TSA at 50, 100, 200, 300, and 500 nmol/L the invasion capability of MG-63 cells decreased significantly compared with the control group (P < 0.05). Mimic hypoxia induced the expression of HIF-1α and VEGF protein. TSA markedly inhibited the expression of HIF-1α and VEGF protein in a dose- and time-dependent manner. Conclusion: The histone deacetylase inhibitor TSA had an significant anticancer activity in vitro and inhibitory effects on the expression of HIF-1α and tumor angiogenesis. It might be a novel anti-cancer agent by targeting HIF-1α and subsequently inhibiting angiogenesis in osteosarcoma.
