Abstract 1569: Antitumor activity of SR16388 against human multiple myeloma in vitro and in vivo

Abstract

Abstract Multiple myeloma (MM) is the cancer of plasma cells that derive from a clonal disorder of terminally differentiated B cells in the bone marrow. MM is generally thought to be refractory against chemotherapeutics and is incurable. Development of novel agents for the treatment of this disease is urgently needed. Previous studies have indicated that MM cells express estrogen receptors (ERs), and anti-estrogens such as ICI 182,780 and Tamoxifen have demonstrated inhibitory effects on proliferation of MM cell lines as well as on MM cells isolated from patients. MM cells also over-express proangiogenic factors such as VEGF to induce angiogenesis and support their growth and survival. At SRI International, we have developed a steroidal anti-angiogenic molecule (SR16388) that potently inhibits angiogenesis in lung and prostate cancers, and it also binds to ER-α and ER-ß with high affinities in the nanomolar range. In this study, we examined the in vitro and in vivo effects of SR16388 on growth of MM cells. In RPMI-8226 multiple myeloma cells, SR16388 inhibited cell proliferation with an IC50 value of 0.9 µM. Cell cycle analysis revealed that SR16388 arrested the RPMI-8226 cells in G2 phase. In an in vivo murine xenograft model, SR16388 significantly inhibited the growth of RPMI-8226 tumors at the dose levels of 50 and 100 mg/kg with P < 0.05 and P < 0.02 respectively in a dose dependent manner. We are currently examining the molecular effects of SR16388 that contribute to its anti-proliferative and anti-angiogenic effects on MM and other human tumor types. Based on our in vitro and in vivo data, we believe that SR16388 is a promising new therapeutic molecule for the treatment of MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1569.