Histone deacetylases inihibitor PCI-24781 induces apoptosis in methotrexate resistant cell line U2-OS/MTX300 in vitro
- Author:
Jun-Qiang YIN
1
Author Information
1. Department of Orthopaedic Oncology
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Histone deacetylase;
Inhibitor;
Methotrexate;
Osteosarcoma
- From:
Chinese Pharmaceutical Journal
2012;47(20):1630-1633
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE: To study the antitumor activity and the related mechanism of histone deacetylase inihibitor PCI-24781 on methotrexate resistant osteosarcoma cell line, U2-OS/MTX300. METHODS: U-20S/MTX300 cells were treated with PCI-24781. Cell viability was evaluated by MTT and colony formation assay. Apoptosis was evaluated by flow cytometry and fluorescent staining. Western Blot was used to detect the expression of apoptosis-related proteins and the acetylated level of histone 3 and 4. RESULTS: PCI-24781 inhibited the viability of U-20S/MTX300 in a concentration-dependent manner. The IC50 value of PCI-24781 on U-20S/ MTX300 at 48 h after administration was (0.55±0.03) μmol · L -1, which was similar to its IC50 value in the MTX sensitive cells (P>0.05). 0.5 μmol · L-1 PCI-24781 treatment could inhibit the colony formation obviously, and the colony inhibit rate was (61±7)%. Typical apoptotie bodies were observed at 48 h after PCI-24781 treatment and the apoptosis rate was (29±4)%. PCI-24781 could induce up-regulation of cleaved-PARP and P53. The acetylated level of histone 3 and 4 were also significantly increased after PCI-24781 treatment. CONCLUSION: Histone deacetylases inihibitor PCI-24781 could inhibit the growth and induce apoptosis in methotrexate resistant osteosarcoma cells. Up-regulation of acetylated histone proteins and P53 are involved in this process.
