A diagram of the proposed mechanism showing anti-tumor effect of TMZ in combination with ZOL against malignant glioma cells expressing MGMT.

According to the results of the present study, ZOL inhibits the activity of Ras and the expression of MGMT in malignant glioma cells and potentiates TMZ-mediated cytotoxicity, inducing growth inhibition and apoptosis of malignant glioma cells that express MGMT and resistant to TMZ. The molecular mechanism leading to the pathway indicated by the dotted arrow remains to be determined.