Investigation of the Mechanism of Angiogenin-Mediated Cancer Cell Proliferation and Tumor Angiogenesis, and Its Application for Cancer Treatment

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In this study, we made an antitumor model of oral cancer by RNAi technology targeting angiogenin, and aimed to elucidate the mechanism of angiogenin-mediated cancer cell proliferation and tumor angiogenesis in order to apply it for cancer treatment.Secreted levels of angiogenin and VEGF in various oral cancer cell lines were measured by ELISA. As a result, HSC-2 cell that secreted high levels of angiogenin and VEGF, and SCCKN cell that secreted low level of angiogenin and high level of VEGF were selected, and transfected with angiogenin RNAi construct. Down-regulation of angiogenin expression by RNAi decreased proliferation in both of the cells in vitro, and resulted in a decrease in 45S ribosomal RNA transcription, ribosome biogenesis and phosphorylation of Akt (Ser473) in HSC-2 cell. Besides, knocking down angiogenin expression in HSC-2 cell strongly decreased tumor volume in athymic mice although it secreted high level of VEGF.These results suggested that angiogenin plays a key role in not only tumor angiogenesis but also cell proliferation in oral cancer. Moreover, angiogenin may be necessary for tumor angiogenesis by VEGF.