The Endocannabinoid System as a Target for Treatment of Breast Cancer
Annual rept. 1 Aug 2008-31 Jul 2009
VIRGINIA COMMONWEALTH UNIV RICHMOND
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During the present funding cycle, we have used in vivo and in vitro approaches to determine whether the endogenous cannabinoid system can be targeted to treat breast cancer. Considerable effort was focused on developing a preclinical model to induce mammary tumors in mice. Oral treatment of the carcinogen, DMBA, led to steady rate of tumors appearance in the mammary region of all female control C57Bl6 mice within approximately 40 weeks. In contrast, tumor development was substantially delayed in female mice lacking fatty acid amide hydrolase FAAH, the primary enzyme responsible for catabolism of the endogenous cannabinoid anandamide. We have excised these tumor cells and have been growing them in culture. Once the cells are verified as adenocarcinoma breast through HE staining, we will evaluate them in in vitro assays of tumor proliferation and invasion, as well as implant them in C57BL6 mice and genetically modified mice to increase throughput of the in vivo experiments. In other studies, we have begun examining the effects of cannabinoids on the proliferation and invasion of the following human breast cell lines Mcf-7, Mcf-10a, and MDA-MB-231. Through these complementary in vivo and in vitro approaches, we will determine whether increasing endocannabinoid signaling has preventative, antiproliferative, or anti-invasion effects on breast cancer, as well as determine the mechanism of action.
- Medicine and Medical Research