CCI-779 plus Cisplatin Is Highly Effective against Human Melanoma in a SCID Mouse Xenotranplantation Model

Abstract

BACKGROUND: This study set out to investigate the antitumor effects of a treatment strategy combining the mTOR inhibitor CCI-779 with cisplatin in vitro and in a human melanoma SCID mouse model. METHODS: In vitro 518A2, Mel-JUSO or 607B cell lines were incubated with CCI-779, cisplatin and CCI-779 plus cisplatin. Based on these results, a 4-group, parallel, controlled experimental study design was initiated in vivo. SCID mice were injected with melanoma cells, and after the development of tumors the mice received daily injections of CCI-779 or solvent. On treatment days 2 and 6 cisplatin or mock solution were administered. RESULTS: In vitro a synergistic antitumor effect was observed for the treatment regimen of CCI-779 plus cisplatin. In SCID mice after 2 weeks of therapy with CCI-779 plus cisplatin 4 of 6 tumors of the 518A2 cell line were completely eradicated. In the two remaining 518A2 xenografts this treatment strategy reduced the tumor weight by 94 +/- 9% compared to solvent. CCI-779 plus cisplatin also exerted a significant antitumor effect in Mel-JUSO and 607B xenografts compared to mock-treated animals. CONCLUSION: We provide circumstantial evidence that the use of CCI-779 plus cisplatin might qualify as a promising strategy in the treatment of human melanoma.