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K. Kimura, Y. Usui, T. Hattori, N. Yamakawa, Y. Okunuki, H. Goto, A. Kaneko, S. Okada, M. Usui, A. Tomoda; In vitro and in vivo Antitumor Effects of a Novel Phenoxazine Derivative on a Human Retinoblastoma Cell Line . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2813.
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© ARVO (1962-2015); The Authors (2016-present)
2–Amino–4,4α–dihydro– 4α,7–dimethyl–3H–phenoxazine–3–one (Phx) is known to have growth–inhibitory effects on various cell lines such as squamous cell carcinoma, adenocarcinoma and leukemia cell lines. In this study, we examined the efficacy of Phx on the proliferation of a human retinoblastoma cell line (Y–79) both in vitro and in vivo.
We evaluated the in vitro effect of Phx on the viability and apoptosis of Y–79 cells using MTT [3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyl tetrazolium bromide] assay. The effect of Phx on apoptosis of Y–79 cells was also evaluated by flow cytometry using annexin–V. The in vivo efficacy of subcutaneous injection of Phx was analyzed histopathologically in BALB/c nude mice inoculated subcutaneously with Y–79 cells.
Phx inhibited the in vitro proliferation of Y–79 cells in a dose–dependent manner. The data obtained by flow cytometry suggest that the mechanism of proliferation inhibition is associated with apoptosis. In vivo, no serious adverse effects were observed in Phx–treated mice compared to the control mice. Phx markedly reduced tumor growth in Y–79–bearing mice. Immunohistochemically, Y–79 tumors in mice treated with Phx showed decreased expression of Mib–1 and p–53, and increased expression in Caspase–9 and Caspase–3, compared with the controls. No significant changes in Bcl–2 were observed in both groups.
Phx demonstrated in vitro and in vivo antitumor activities against Y–79, probably by inhibiting cell growth and inducing apoptosis. Phx may be a useful antitumor drug in the treatment of retinoblastoma.
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