• Hisataka Kitano, Atsushi Mamiya, Tomomi Ishikawa, Yusuke Fujiwara, Yoh Masaoka, Toshio Miki, and Chiaki Hidai.
• Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan.
• Rev Invest Clin. 2020 May 7; 73 (1): 039-051.

BackgroundCancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have longterm effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model.ObjectiveIn this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors.Materials And MethodsMouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis.ResultsAll mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins.ConclusionThese findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis.

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