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�� ��mol��L-1�� which was similar to its IC50 value in the MTX sensitive cells (P>0.05). 0.5 ��mol��L-1 PCI-24781 treatment could inhibit the colony formation obviously�� and the colony inhibit rate was (61��7)%. Typical apoptotic 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.
YIN Jun-Qiang,
XIE Xian-Biao,
ZOU Chang-Ye etc
.Histone Deacetylases Inihibitor PCI-24781 Induces Apoptosis in Methotrexate Resistant Cell Line U2-OS/MTX300 in Vitro[J] Chinese Pharmaceutical Journal, 2012,V47(20): 1630-1633
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