Cytotoxicity of human prostate cancer cell lines in vitro and induction of apoptosis using 213Bi-Herceptin alpha-conjugate.

Abstract

HER-2 has been implicated in the oncogenesis of human prostate cancer (CaP) and is the target of a new treatment for metastatic breast cancer using the humanised monoclonal antibody (MAb) trastuzumab (Herceptin). In this study, a novel alpha-particle emitting [213Bi]Herceptin construct, which targets the HER-2 extracellular domain on CaP cells, was prepared and evaluated in vitro. We used immunocytochemistry, flow cytometry and Western blot analysis to examine the expression of HER-2 in a panel of established human CaP cell lines, used the MTS assay to evaluate the cytotoxicity of 213Bi-Herceptin on these cell lines and the TUNEL assay to document apoptosis. The results indicate that LNCaP-LN3 cells express high levels of HER-2 protein, in contrast, DU 145 cells express low to medium levels, and PC-3 cells express an undetectable level of HER-2 protein. 213Bi-Herceptin was specifically cytotoxic to LNCaP-LN3 cells in a concentration-dependent fashion, cause the cells to undergo apoptosis, whereas DU 145 showed an HER-2 level-dependent response to 213Bi-Herceptin cytotoxicity. In contrast, PC-3 cells were resistant to 213Bi-Herceptin-induced cytotoxicity. The 213Bi-Herceptin induced apoptosis in LNCaP-LN3 cells could be inhibited by incubation with unlabeled Herceptin. Our results suggest that 213Bi-Herceptin alpha-conjugate might be a promising new agent for the treatment of preangiogenic cancer cell clusters or micro-metastases with high levels of HER-2 expression.

• Authors: Yong Li, Paul J Cozzi, Chang F Qu, David Y Zhang, Syed M Abbas Rizvi, Chand Raja, Barry J Allen
• Journal: Cancer letters (Cancer Lett) Vol. 205 Issue 2 Pg. 161-71 (Mar 18 2004) ISSN: 0304-3835 [Print] Ireland
• PMID: 15036648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Radioisotopes
• Receptor, ErbB-2
• Trastuzumab
• Bismuth

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Apoptosis (radiation effects)
• Bismuth (therapeutic use)
• Cell Line, Tumor
• Humans
• Male
• Prostatic Neoplasms (pathology, radiotherapy)
• Radioimmunotherapy
• Radioisotopes (therapeutic use)
• Receptor, ErbB-2 (analysis)
• Trastuzumab