Abstract 2353: Therapeutic effect of cilengitide in combination with CKD-602, a campothecin derivative, against experimental glioblastoma

Abstract

The prognosis and the clinical course for glioblastoma patients remain dismal in spite of various multidisciplinary approaches of treatment, such as concurrent chemoradiotherapy with temozolomide. Especially, the resistance to temozolomide of primary or recurrent glioblastoma is the significant obstacle to the cure of this tumor. In the present study, we evaluated the in vitro and in vivo antitumor effect of cilengitide in combination with CKD-602, a camptothecin derivate, for experimental glioblastoma. The combination treatment with cilengitide and CKD-602 enhanced the cytotoxic effects to the glioblastoma cell lines, including U87MG and U251MG and increased the proportion of apoptosis of the tumor cells, compared with the monotherapy with either drug. Nude mice with established U87MG glioblastoma were assigned to the 4 groups; control group (injection with saline only), 2 cilengitide group (injection with a dose of cilengitide at 2 mg/mL), CKD-602 group (injection with a dose of CKD-602 at 2 mg/mL), and combination group. In animals with combination therapy, the significant reduction of tumor volume was demonstrated (p < 0.05). The immunohistochemistry with CD31 and Annexin-V showed that this synergistic effect was caused by the decrease of angiogenesis by cilengitide and the increase of apoptosis by CKD-602. Cilengitide in combination with CKD-602 could be an alternative treatment option for glioblastoma. Keywords; glioblastoma; cilengitide; CKD-602; angiogenesis; apoptosis Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2353. doi:1538-7445.AM2012-2353