Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo

32Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

In this study, we investigated the in vitro and in vivo efficacy of patupilone (epothilone B, EPO906), a novel nontaxane microtubule stabilizing agent, in treatment of multiple myeloma (MM). Patupilone directly inhibited growth and survival of MM cells, including those resistant to conventional chemotherapies, such as the taxane paclitaxel. Patupilone induced G2M arrest of MM cells, with subsequent apoptosis. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1), 2 known growth and survival factors for MM, did not protect MM.1S cells against patupilone-induced cell death. Proliferation of MM cells induced by adherence to bone marrow stromal cells (BMSCs) was also inhibited by patupilone and was paralleled by down-regulation of vascular endothelial growth factor (VEGF) secretion. Importantly, stimulation of cells from patients with MM, either with IL-6 or by adherence to BMSCs, enhanced the anti-proliferative and proapoptotic effects of patupilone. Moreover, patupilone was effective against MM cell lines that overexpress the MDR1/P-glycoprotein multidrug efflux pump. In addition, patupilone was effective in slowing tumor growth and prolonging median survival of mice that received orthotopical transplants with MM tumor cells. Taken together, these preclinical findings suggest that patupilone may be a safe and effective drug in the treatment of MM, providing the framework for clinical studies to improve patient outcome in MM. © 2005 by The American Society of Hematology.

Cite

CITATION STYLE

APA

Lin, B., Catley, L., LeBlanc, R., Mitsiades, C., Burger, R., Tai, Y. T., … Anderson, K. C. (2005). Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo. Blood, 105(1), 350–357. https://doi.org/10.1182/blood-2004-06-2499

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free