IDH1 Overexpression Induced Chemotherapy Resistance and IDH1 Mutation Enhanced Chemotherapy Sensitivity in Glioma Cells in Vitro and in Vivo


Isocitrate dehydrogenase (IDH) is of great importance in cell metabolism and energy conversion. IDH mutationin glioma cells is reported to be associated with an increased overall survival. However, effects biological behaviorof therapy of gliomas are unclear. Here, we investigated the influence of wild-type and mutated IDH genes onglioma cell biological behavior and response to chemotherapy. Relevant mechanisms were further explored.We designed our study on the background of the IDHR132H mutation. Stable cell lines were constructed bytransfection. The CCK-8 method was used to assess cell proliferation, flow cytometry for the cell cycle andcell apoptosis, and the transwell method for cell invasion. Nude mouse models were employed to determinetumorigenesis and sensitivity to chemotherapy. Western blotting was used to detect relevant protein expressionlevels. We found that overexpression of wild IDH1 gene did not cause changes in the cell cycle, apoptosis andinvasion ability. However, it resulted in chemotherapy resistance to a high dose of temozolomide (TMZ) in vivoand in vitro. The IDH1 mutation caused cell cycle arrest in G1 stage and a reduction of proliferation and invasionability, while raising sensitivity to chemotherapy. This may provide an explanation for the better prognosis ofIDH1 mutated glioma patients and the relative worse prognosis of their wild-type IDH1 counterparts. We alsoexpect IDH1 mutations may be optimized as new targets to improve the prognosis of glioma patients.