Effects of a Viral Peptide (Nef) on Growth and Metastasis of Human Breast Cancer
Annual rept. 1 Sep 2008-31 Aug 2009
MOREHOUSE SCHOOL OF MEDICINE ATLANTA GA
Pagination or Media Count:
We have shown that a novel peptide from HIV-1 Nef NefM1 induces apoptosis through the CXCR4 receptor. We would like to exploit this as a cancer therapeutic agent. Breast cancer cell lines, MDA-MB231 231, MDAMB468 468, MCF-7, DU4475, and HMEC were each evaluated for their response to NefM1. Apoptosis was assessed using TUNEL staining and caspase-3 activation. The presence of CXCR4 receptors on the tumor cells was determined using immunohistochemistry and PCR analyses. Xenografts derived from CXCR4 cells were propagated in SCID mice and evaluated for the persistence of the receptor and the effects of NefM1 on growth and metastasis. The growing tumors underwent volumetric measurements weekly. and comparisons were made between those treated with NefM1 biweekly, by i.p. injections, and those untreated. Results. Breast cell lines that were positive for CXCR4 receptors all underwent apoptosis when treated with Nef, as did those CXCR4-negative cells that were transfected with CXCR4. Breast xenografts derived from 231 cells demonstrated smaller primaries and significantly smaller metastatic tumors in the Nef treated group. Conclusion. NefM1 causes apoptotic reduction in vitro and in vivo growth of breast cancer cells and tumor xenografts, respectively.
- Anatomy and Physiology
- Medicine and Medical Research