Chih Jen YangChi Te KuoLi Hsien WuMan Chin ChenChristian Ronquillo PangilinanNaphichaya PhacharapiyangkulWangta LiuYa Huey ChenChe Hsin LeeKaohsiung Medical University Chung-Ho Memorial HospitalChina Medical University Hospital TaichungMahidol UniversityKaohsiung Medical UniversityNational Sun Yat-Sen University TaiwanChina Medical University TaichungNational Cheng Kung University Medical College2020-01-272020-01-272019-01-01International Journal of Medical Sciences. Vol.16, No.5 (2019), 636-643144919072-s2.0-85067099569https://repository.li.mahidol.ac.th/handle/20.500.14594/52383© Ivyspring International Publisher. Chemotherapy is now in common use for the treatment of tumors; however, with tumor growth retardation comes the severe side effects that occur after a chemotherapy cycle. Eicosapentaenoic acids (EPA) used in combination with chemotherapy has an additive effects and provides a rationale for using EPA in tandem with chemotherapy. To improve the efficacy and safety of this combination therapy, a further understanding that EPA modulates with the tumor microenvironment is necessary. Connexin 43 (Cx43) is involved in enhancing chemosensitivity that was suppressed in a tumor microenvironment. We aim to investigate the role of EPA in chemosensitivity in murine melanoma by inducing Cx43 expression. The dose-dependent upregulation of Cx43 expression and gap junction intercellular communication were observed in B16F10 cells after EPA treatment. Furthermore, EPA significantly increased the expression levels of mitogen-activated protein kinases (MAPK) signaling pathways. The EPA-induced Cx43 expression was reduced after MAPK inhibitors. Knockdown Cx43 in B16F10 cells reduced the therapeutic effects of combination therapy (EPA plus 5-Fluorouracil). Our results demonstrate that the treatment of EPA is a tumor induced Cx43 gap junction communication and enhances the combination of EPA and chemotherapeutic effects.Mahidol UniversityMedicineArticleSCOPUS10.7150/ijms.30889