EXTH-23. COMBINED EFFECTS OF NICLOSAMIDE AND TEMOZOLOMIDE AGAINST HUMAN GLIOBLASTOMA TUMORSPHERES

Abstract PURPOSE Glioblastoma (GBM) is the most aggressive type of brain tumor and has poor survival outcomes, even after a combination of surgery, radiotherapy, and chemotherapy. Temozolomide is the only agent that has been shown to be effective against GBM, suggesting that combination of temozolomide with other agents may be more effective. Niclosamide, an FDA approved anthelmintic agent, has shown anti-cancer effects against human colon, breast, prostate cancers as well as GBM. However, the efficacy of the combination of niclosamide with temozolomide against GBM tumorspheres (TSs) has not been determined. We hypothesized that the combined treatment could effectively suppress GBM TSs. METHODS Effects of niclosamide and/or temozolomide on GBM TSs were evaluated. Viability, stemness, and invasive properties of GBM TSs were examined. In vivo anticancer efficacy was tested in a mouse orthotopic xenograft model. RESULTS The combination of niclsoamide and temozolomide significantly inhibited the viability, sphere formation, expression of stemness-related proteins, and invasive properties of GBM TSs. This combination significantly down-regulated the expression of epithelial mesenchymal transition-related proteins. Bioluminescence imaging further showed that compared with either agent alone, combination of niclosamide and temozolomide significantly reduced the tumor burden in orthotopic xenograft models. CONCLUSIONS The combination of niclosamide and temozolomide effectively decreased the stemness and invasive properties of GBM TSs, suggesting that this regimen may be therapeutically effective in treating patients with GBM. KEYWORDS: Glioblastoma; Invasion; Niclosamide; Temozolomide; Tumorsphere