The novel sigma-2 receptor ligand SW43 stabilizes pancreas cancer progression in combination with gemcitabine

Molecular Cancer

Research

Dirk Spitzer¹  Jonathan B Mitchem¹  John R Hornick¹  Peter Goedegebuure²  William G Hawkins²  Suwanna Vangveravong³  Robert H Mach³  Zhude Tu³  Jinbin Xu³ 

[1] Department of Surgery, Washington University School of Medicine, S. Euclid Avenue, St. Louis, MO, USA;Department of Surgery, Washington University School of Medicine, S. Euclid Avenue, St. Louis, MO, USA;Alvin J. Siteman Cancer Center, Washington University School of Medicine, S. Euclid Avenue, St. Louis, MO, USA;Division of Radiology, Washington University School of Medicine, St. Louis, MO, USA;

关键词: Pancreatic Cancer;    Gemcitabine;    Pentazocine;    Panc02 Cell;    Pancreas Cancer;   

DOI  :  10.1186/1476-4598-9-298

 received in 2010-07-19, accepted in 2010-11-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSigma-2 receptors are over-expressed in proliferating cancer cells, making an attractive target for the targeted treatment of pancreatic cancer. In this study, we investigated the role of the novel sigma-2 receptor ligand SW43 to induce apoptosis and augment standard chemotherapy.ResultsThe binding affinity for sigma-2 ligands is high in pancreas cancer, and they induce apoptosis with a rank order of SV119 < SW43 < SRM in vitro. Combining these compounds with gemcitabine further increased apoptosis and decreased viability. Our in vivo model showed that sigma-2 ligand treatment decreased tumor volume to the same extent as gemcitabine. However, SW43 combination treatment with gemcitabine was superior to the other compounds and resulted in stabilization of tumor volume during treatment, with minimal toxicities.ConclusionsThis study shows that the sigma-2 ligand SW43 has the greatest capacity to augment gemcitabine in a pre-clinical model of pancreas cancer and has provided us with the rationale to move this compound forward with clinical investigations for patients with pancreatic cancer.

【 授权许可】

Unknown   
© Hornick et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.