title: PTD4-apoptin protein and dacarbazine show a synergistic antitumor effect on B16-F1 melanoma in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jia-lu
authors.initials: JL
authors.lastname: Jin
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.forename: Tie-jun
authors.initials: TJ
authors.lastname: Yin
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Lu
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Xia
authors.forename: Yu-yuan
authors.initials: YY
authors.lastname: Xie
authors.forename: Yong
authors.initials: Y
authors.lastname: Di
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.forename: Jian-li
authors.initials: JL
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Mathieu H M
authors.initials: MH
authors.lastname: Noteborn
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000737:chemistry*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D036022:Capsid Proteins; C557704:PTD4-apoptin protein; D011993:Recombinant Fusion Proteins; C091717:VP3 protein, Chicken anemia virus; D003606:Dacarbazine