Herceptin-Resistance and Overexpression of Anti-Apoptotic Molecule Bci-XL: A Potential Strategy for Overcoming Resistance to Herceptin
Abstract
The major goal of this Concept Award project is to investigate whether a small molecule inhibitor of Bcl-xL will be able to overcome the resistance of Her-2/neu-(+) breast cancer cells to Herceptin. (-)-gossypol showed potent anti-tumor activity to human breast cancer cell lines with high levels of Bcl-xL but has only minimal effect on human normal breast epithelial cells with low Bcl-xL. (-)-gossypol potently enhanced growth inhibition and apoptosis induction by doxorubicin and docetaxel the currently used chemotherapeutic agents for breast cancer. However interaction of (-)-gossypol with Herceptin activity in Her-2(+) breast cancer cells are still ongoing. Bcl-xL knockdown by siRNA abolished the tumorigenecity of Her-2(+) MCF-7 cells. The data support that Bcl-xL plays a critical role in breast cancer initiation progression and chemoresistance but its role in Herceptin resistance remains to be further elucidated. The study provide us a solid foundation to develop (-)-gossypol as a novel molecular targeted therapy for the treatment of breast cancer with Bcl-xL overexpression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA453404
Entities
People
- Liang Xu
Organizations
- University of Michigan