The effect of fish oil on chemotherapy activity in mice: Clinical implications.

Abstract

10532 Background: Environment-mediated resistance to chemotherapy is emerging as a cause of treatment failure. In mouse models, we showed that mesenchymal stem cells (MSCs) are activated by platinum-based chemotherapy to secrete two unique platinum-induced fatty acids (PIFAs): KHT(n-6) and 16:4(n-3) which induce resistance to a broad spectrum of chemotherapies. These fatty acids are also present in various food products and supplements. Fish oil and some algae are frequently used by cancer patients because of their perceived positive health effects. Therefore, we hypothesized that the use of fish oil and specific algae containing PIFAs may have an adverse effect on the anti-tumor effects of chemotherapy. Methods: Two different mouse tumor models were established in which we investigated whether co-administration of orally administered PIFAs, fish oil products and algae extracts influenced the response to chemotherapy. Results: We found that our identified PIFAs are abundantly present in commercially available fish oil products (0.4-0.6uM 16:4(n-3)) and algae extracts (27uM 16:4(n-3)). First we tested whether the purified PIFAs induced resistance when administered orally. We found that orally administered, pure PIFAs induced resistance to cisplatin in both our tumor models; mean tumor volume after cisplatin 71 mm3 (SEM 5) vs 233 mm3 (SEM 44) after cisplatin plus PIFAs. Next, we fed tumor-bearing mice two types of commercially available fish oils or algae extracts and treated them with cisplatin. A single oral dose of 100ul of two different commercially available fish oil products or algae extracts resulted in neutralization of the anti-tumor effects of cisplatin in two models; cisplatin 71 mm3 (SEM 5) vs cisplatin + fish oil 294 mm3 (SEM 49). Orally administered EPA, the main component of most fish oil products, which served as a control, had no effect on response to chemotherapy. Conclusions: Commercially available fish oil and algae extracts can induce resistance to chemotherapy at doses similar to the advised daily dose in humans. The use of these products during chemotherapy treatment should therefore be avoided. These results support the clinical relevance of these PIFAs in the development of resistance to chemotherapy.