Flavopiridol's antiproliferative effects in glioblastoma multiforme

Glioblastoma multiforme (GBM) is largely refractory to surgical operation, radiotherapy, and chemotherapy in use today. Remaining lifetime accounting for the GBM-affected patients varies between 12 and 16 months generally. The most frequently altered genes in GBM are p53, epidermal growth factor receptor, PTEN, and cyclin-dependent kinase inhibitor 2A. Our aim is to investigate the antiproliferative and apoptotic effects of flavopiridol, a cyclin-dependent kinases and specific phosphokinase inhibitor, on glioblastoma cell lines having different genetic profiles: U87MG, U118MG, and T98G.

Cell viability and IC50 values were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, protein expressions were determined by Western blot and caspase activities were analyzed by activity kit.

Western blot analysis showed down-regulation of the cyclin D1, c-Myc, and p53 protein activities, and up-regulation of p27KIP1 activity after flavopiridol treatment. Additionally, flavopiridol diminished p-Akt protein levels generally which induces inhibition of proliferation.

The present study demonstrated that flavopiridol did not induce caspase-3/7 activation, BIM, and BAX pro-apoptotic proteins but it leads to the expression changes of various proteins that inhibit proliferation and eternity in glioblastoma cell lines which have different genetic alterations.