PTD4-apoptin protein enters cells and harbors tumor-selective cell death activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose-dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of drug interaction < 1) in all three different tumor cell lines. In vivo, PTD4-apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1 melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment significantly increased the antitumor effect in comparison to the single treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a 50% reduction of dacarbazine revealed similar antitumor activities, without detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine treatment represents a promising novel efficient and safe anticancer strategy. © 2010 Elsevier B.V. All rights reserved.
Jin, J. L., Gong, J., Yin, T. J., Lu, Y. J., Xia, J. J., Xie, Y. Y., … Qu, S. (2011). PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo. European Journal of Pharmacology, 654(1), 17–25. https://doi.org/10.1016/j.ejphar.2010.12.004