## 5 Studies and Mechanism about n-3 PUFAs and Melanoma
### Discrepancy in Results and Approaches to Studies in Humans

Table 1: \(Cont.\)
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Model** & **Dose** & **Results** & **Reference** \\ \hline In vivo (Fat-1 C57 BL/6 transgenic & 50 uM AA, 50 uM AA plus 50 uM indomethacin, 50 uM & - Inhibition of PTEN in the tumor and surrounding tissues of Fat-1 mice & \\ mice with implantation of B16 & EPA, and 50 uM indomethacin & - AA (50 uM) did not affect cell growth & [161] \\ melanoma cells) & 50 uM indomethacin & - EPA (50 uM) exhibited an inhibitory effect on the growth of melanoma cells. This growth-inhibitory effect could be blocked by the presence of 50 uM indomethacin & \\ \hline In vivo (Fat-1 C57 BL/6 transgenic & 50 g wheat starch, 0.3 g & - No significant difference in the levels of PGE2 & \\ mice with implantation of B16-F10 melanoma cells) & - The protein expression levels of E-cadherin was upregulated and N-cadherin were downregulated in the tumor tissues of fat-1 mice & \\ In vivo (Fat-1 C57 BL/6 transgenic & 50 g wheat starch, 0.3 g & - Fat-1 mouse tumor tissues exhibited a decrease in NF-kB and STAT3 than those from WT mice & \\ mice with implantation of B16-F10 melanoma cells) & - After VitF supplementation, no significant difference in the levels of MDA was observed between fat-1 and WT mice, however, fat-1 mice exhibited decreased tumor growth compared with WT-mice & \\  & 100 IU/kg VitFiva oral & - Fat-1 tumor tissues exhibited a marked decrease in the expression levels of \(\beta\)-catenin and c-Myc compared with those from WT mice & \\ \hline In vivo (Fat-1 C57 BL/6 transgenic & 500 mg/mL 18-HEPE (a n-3 & - Pulmonary metastasis & \\ mice with implantation of B16-F0 melanoma cells) & - Algal oil treatment inhibited lung metastases of B16-F10 & \\  & 100 mg/mL 18-HEPE (a n-3 & - Pulmonary metastasis & \\  & EPA-derived lipid mediator) & of melanoma B16-F0 cells is significantly reduced in Fat-1 & \\ In vivo (Fat-1 C57 BL/6 transgenic & 500 mg and 1 mg of 18-HEPE & -18-HEPE directly repressed CXCR4 expression of B16-F0 cells & \\ mice with implantation of B16-F0 melanoma cells) & - Higher lung TGF8 expression & \\  & 100 mg/mL 18-HEPE (a n-3 & - Pulmonary metastasis & \\  & 100 mg/mL  
search is needed to elucidate the precise molecular mechanisms through which PUFAs exert their therapeutic effects, including their role in modulating inflammation, gene expression, cell signaling pathways, lipomics and apoptosis. Investigating how PUFAs interact with other cancer treatments such as chemotherapy, immunotherapy and radiotherapy could enhance their effectiveness and reduce side effects. Moreover, nowadays the majority of the results are based on in vitro and in vivo models. Indeed, long-term, large-scale clinical trials are necessary to confirm the benefits of PUFAs in cancer prevention and treatment and establish optimal dosages, treatment durations and the most effective forms of PUFAs. Currently, medicine is changing its approach to treating people due to scientific and biotechnological advances. Personalized medicine is now taking on a highly important role, where treatments are tailored to the patient's metabolism, optimizing results. Exploring the potential of PUFAs as part of personalized medicine, where dietary interventions are based on an individual genetic makeup, type of cancer and metabolic and lipomics profile, is also critical. It is known that PUFAs interact with other bioactive compounds. The integration of PUFAs into broader dietary interventions and lifestyle modifications could enhance overall health and reduce cancer risk. For this reason, it is also important to develop predictive biomarkers to identify which patients are most likely to benefit from PUFA supplementation, and using biomarkers to monitor treatment effectiveness and adjust protocols is another important direction which could involve new inflammation or oxidation markers. Research should also focus on the role of PUFAs in various types of cancer, including both common and rare cancers, and their potential in prevention through epidemiological studies and clinical trials.