Newcastle disease virus enhances the growth-inhibiting and proapoptotic effects of temozolomide on glioblastoma cells in vitro and in vivo
ABSTRACT
Glioblastoma (GBM) is the most serious and most common brain tumor in humans. Despite recent advances in the diagnosis of GBM and the development of new treatments, the prognosis of patients has not improved. Multidrug resistance, particularly resistance to temozolomide (TMZ), is a challenge in combating glioma, and more effective therapies are needed. Complementary treatment with the LaSota strain of the naturally oncolytic Newcastle disease virus (NDV-LaSota) is an innovation. In our experiments, the combination therapy of NDV-LaSota and temozolomide (TMZ) was more effective than either treatment alone in inducing apoptosis in glioma cells. NDV can function as a tumor cell selective approach to inhibit AKT and activate AMPK. Consequently, mTOR, 4EBP1 and S6K were also suppressed. The combination therapy of NDV and TMZ also significantly extended survival in a rat xenograft tumor model. In conclusion, NDV suppress AKT signaling and enhances antitumor effects of TMZ. Our study provides one of the theoretical basis for the use of a combined therapy of TMZ and NDV, which could benefit GBM patients.