Paclitaxel-induced G2/m arrest via different mechanism of actions in glioma cell lines with differing p53 mutational status

Abstract

A major concern with regard to glioma treatment arises from the fact that high-grade gliomas are insensitive to the majority of anticancer therapies. The aim of the present study was to investigate anti-proliferation potential of the mitotic inhibitor paclitaxel in three glioma cells with different BRAF mutation status. The U-87-MG cells were found to be more resistant to paclitaxel than other two glioma cell lines T98G and DBTRG-05MG, suggesting that the response of glioma cells to paclitaxel is not affected by the BRAF genotype. In addition, despite the induction of both apoptosis and autophagy in all glioma cell lines tested, our study has not specifically addressed the correlation of apoptosis and autophagy induction with growth inhibition. Instead, we found that paclitaxel caused a remarkably significant G2/M arrest in response to paclitaxel in T98G and DBTRG-05MG cells, whereas, less significant G2/M arrest was detected after paclitaxel treatment in U-87-MG, which exhibited more resistant to paclitaxel than other two cell lines. It is observed that T98G cells with mutant p53 progress through G0/G1 checkpoint and greatly accumulated in the subsequent G2/M phase. In case of DBTRG-05MG cells with wild type p53, paclitaxel-induced growth inhibition displayed characteristics of p27Kip1-dependent G2/M arrest. In this study data suggest that paclitaxel-induced growth inhibition of glioma cells is tightly correlated with the G2/M arrest regardless of p53 mutation status.