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

INTRODUCTION: Glioblastoma 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.
METHODS: The 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.
RESULTS: Compared 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.
CONCLUSIONS: Ultrasound enhanced anti-tumor effect of temozolomide in glioblastoma cells via JNK and p38 pathways. © Biomedical Engineering Society 2018.