Combination Therapy of Temozolomide, Ribavirin and Interferon-Beta for Glioblastoma In Vivo

Abstract

We have investigated the potential of the antiviral drugs ribavirin (RBV) and interferon-beta (IFN-β) for drugrepositioning and have described the antitumor effect of combination therapy of temozolomide (TMZ), RBV andIFN-β for glioblastoma (GBM) cells in vitro. However, sufficient data, including in vivo experiments for clinicalapplication, are incomplete. We conducted both in vitro and in vivo experiments to validate the antitumor effect of TMZ, RBV and IFN-β combination therapy on the commercialized human GBM cell line U-87MG and the originally established patient-derived GBM cell line 0125-GSC. In vitro experiments counting viable U-87MG and0125-GSC cells after combined administration of TMZ and RBV and/or TMZ, RBV and IFN-β indicated that cellproliferation was strongly inhibited by both combination therapies compared to single drugs. However, no significant difference was found between these combination therapies. The expression of apoptosis-related proteins wasenhanced after the combined administration of TMZ and RBV and/or TMZ, RBV and IFN-β compared with theadministration of single drugs. In vivo experiments implanted U-87MG cells into nude mouse brains, and singledrugs or combination therapy were administered. Survival time in mice was significantly prolonged by systemictreatment with combination therapy of TMZ and RBV and/or TMZ, RBV and IFN-β compared to single drugtreatment, but no significant difference was found between the two combination therapies. The present resultsdemonstrated that TMZ, RBV and IFN-β and/or TMZ and RBV combination therapy showed antitumor effectsagainst GBM cells both in vitro and in vivo. TMZ and RBV combination therapy may be the most promisingnovel treatment for clinical application.