Omega-6 Polyunsaturated Fatty Acids Enhance Tumor Aggressiveness in Experimental Lung Cancer Model: Important Role of Oxylipins

Lung cancer is currently the leading cause of cancer death worldwide; it is often diagnosed at an advanced stage and bears poor prognosis. It has been shown that diet is an important environmental factor that contributes to the risk and mortality of several types of cancers. Intake of omega-3 and omega-6 PUFAs plays an important role in cancer risk and progression. Current Western populations have high consumption of omega-6 PUFAs with a ratio of omega-6/omega-3 PUFAs at 15:1 to 16.7:1 This high consumption of omega-6 PUFAs is related to increased cancer risk and progression. However, whether a diet rich in omega-6 PUFAs can contribute to tumor aggressiveness has not been well investigated. We used a murine model of pulmonary squamous cell carcinoma to study the aggressiveness of tumors in mice fed with a diet rich in omega-6 PUFAs and its relationship with oxylipins. Our results shown that the mice fed a diet rich in omega-6 showed a marked increase in proliferation, angiogenesis and proinflammatory markers and decreased expression of pro-apoptotic proteins in their tumors. Oxylipin profiling revealed an upregulation of various pro-tumoral oxylipins including PGs, HETEs, DiHETrEs and HODEs. These results demonstrate for the first time that high intake of omega-6 PUFAs in the diet enhances the malignancy of tumor cells by histological changes on tumor dedifferentiation and increases cell proliferation, angiogenesis, pro-inflammatory oxylipins and molecular aggressiveness targets such as NF-kappa B p65, YY1, COX-2 and TGF-beta.

Automated summary

Lung cancer is the leading cause of cancer death worldwide, and the intake of omega-6 polyunsaturated fatty acids (PUFAs) in the diet is associated with increased cancer risk and progression. This study found that a diet rich in omega-6 PUFAs enhances the malignancy of tumor cells, promoting cell proliferation, angiogenesis, and inflammation.