Ultrasound Enhanced Anti-tumor Effect of Temozolomide in Glioblastoma Cells and Glioblastoma Mouse Model

Abstract

IntroductionGlioblastoma is the most aggressive cancer that begins within the brain. In clinic, temozolomide was used as anti-tumor drugs for glioblastoma chemotherapy, but showed limited effect. Therefore, how to improve the effect of temozolomide to glioblastoma is urgently needed.MethodsThe cell viability of T98G cells was detected by cell counting kit-8 (CCK-8) assay. Apoptosis was detected using the Annexin-V-FITC & PI apoptosis kit and assessed by flow cytometry. The expression levels of Bax, B cell lymphoma 2 (Bcl-2), phos-Jun N-terminal kinases (JNK), phos-extracellular signal–regulated kinases (ERK) and phos-p38 were determined by western blot. The effect of ultrasound and temozolomide combination in mice was determined by survival analysis.ResultsCompared with temozolomide treatment alone, ultrasound and temozolomide combination inhibited the cell viability, and promotes apoptosis of human glioblastoma T98G cells. Bax level increased, while Bcl-2 level decreased in combination group. Mechanically, combination treatment promoted apoptosis via JNK and p38 pathways. In mouse glioblastoma model, combination treatment improved overall survival.ConclusionsUltrasound enhanced anti-tumor effect of temozolomide in glioblastoma cells via JNK and p38 pathways.