Dietary Fish Oil Deactivates a Growth-Promoting Signaling Pathway in Hepatoma 7288CTC in Buffalo Rats

Abstract

Abstract: Dietary fish oil decreases growth of solid tumors in rodents. Mechanisms for this effect are not well defined. In rat hepatoma 7288CTC, short-term (1–2 h) treatment with eicosapentaenoic acid during perfusion in situ reduced fatty acid uptake and [³H]thymidine incorporation. To determine if dietary fish oil had this effect in vivo, 48 male Buffalo rats were implanted with tissue-isolated hepatoma 7288CTC and were divided into three groups: Diet I (8% olive oil/2% corn oil), Diet II (6% olive oil/2% corn oil/2% fish oil), or Diet III (3% olive oil/3% corn oil/4% fish oil).When tumors weighed 4 to 6 g rats were anesthetized and tumor fatty acid uptake and 13-hydroxyoctadecadienoic acid release were measured in vivo by arterial minus venous differences. Tumors were analyzed for cyclic adenosine monophosphate (cAMP), DNA content, and [³H]thymidine incorporation. Fish oil feeding significantly (P < 0.05) reduced tumor growth, cAMP content, fatty acid uptake, 13-hydroxyoctadecadienoic acid formation, DNA content, and [³H]thymidine incorporation. Addition of either pertussis toxin or 8-bromoadenosine-cAMP to the arterial blood reversed the inhibitions in tumors in rats fed diet II. These results provide in vivo evidence that dietary fish oil suppressed a specific linoleic acid-dependent, inhibitory G protein-coupled, growth-promoting signaling pathway in rat hepatoma 7288CTC.