Muscle Contraction Arrests Tumor Growth
Abstract
Early research indicates that a factor released from contracting muscles causes tumor regression. We have repeatedly observed that exercise slows tumor growth rate, resulting in smaller tumors. We will examine the hypothesis that a tumoristatic factor is released by contracting muscles. Soleus (slow-oxidative) and flexor digitorium brevis (fastglycolytic) muscles of Wistar rats will be excised, maintained in Krebs Heinsleit buffer, and attached by electrodes to a force transducer. To fatigue, moderate, and no stimulation protocols will be performed to test a dose response effect. The buffer and effluent from individual muscles will be dialyzed, lyophilized and resuspended in saline. Extracts will be tested for growth effects in MCF-7 and MDA-MB-231 cells using 5-bromo-2-deoxyuridine incorporation and TUNEL assays. Growth-inhibiting and control extracts will be injected subcutaneously into female BALB/c nude mice, implanted with ER+ or ER- breast tumor cells, after tumors have reached 1 cm3. Tumor size will be measured 3 times/week and animals sacrificed after 2-6 weeks. Tumors will be excised, weighed, then portions frozen and fixed to determine proliferation and apoptotic indices. Extract aliquots will be frozen at -80 C for future characterization of the tumoristatic factor(s). This work has important implications for prevention and treatment of breast cancer, including: identification of a mechanism for exercise-mediated tumor inhibition, identification of a marker to assess efficacy of an exercise program to inhibit tumorigenesis, and identification of a therapeutic intervention, using the tumoristatic factor pharmacologically, or through an exercise program to release the factor into circulation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA572645
Entities
People
- Kim Westerlind
Organizations
- University of Colorado Health