Clinically, temozolomide (TMZ) is widely used in glioblastoma (GBM) treatment. However, the toxicity of TMZ may influence the quality of patient life. Thus, novel treatment options for sensitizing GBM cells to TMZ chemotherapy are necessary. Aurora-A is widely expressed in GBM and correlated with poor prognosis. It has been proven to be an effective target for gene therapy and chemotherapy. In the present study, short hairpin (sh)RNA targeting Aurora-A was employed to knockdown Aurora-A expression in GBM cells. Cell Counting Kit-8 assays, flow cytometry, colony formation assays, invasion assays and tube formation assays were used to determine the effects of Aurora-A knockdown when combined with TMZ treatment. A U251 subcutaneous cancer model was established to evaluate the efficacy of combined therapy. The results of the present study indicated that the proliferation, colony formation, invasion and angiogenesis of GBM cells were significantly inhibited by combined therapy when compared with TMZ treatment alone. In vivo results demonstrated that knockdown of Aurora-A significantly (P=0.0084) sensitizes GBM cells to TMZ chemotherapy. The results of the present study demonstrated that knockdown of Aurora-A in GBM cells enhances TMZ sensitivity in vitro and in vivo. Therefore, Aurora-A knockdown may be a novel treatment option for decreasing TMZ toxicity and improving patient quality of life.
Oncology letters. 2016 Oct 14 [Epub]
Jing Gan, Fangfang Wang, Dezhi Mu, Yi Qu, Rong Luo, Qiu Wang
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China; Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan 610041, P.R. China., Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.