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The combined use of currently used anticancer genotoxins with other drugs is a therapeutic tool for potentially increasing the efficacy of the genotoxins. In the present study, the effects of a RasGAP-derived peptide, P110 (RasGAP301-316), designed to target Ras-GTPase activating protein SH3 domain-binding proteins (G3BPs), on the chemotherapeutic agent, cisplatin (DDP), were examined. P110 was demonstrated to enhance the effect of DPP in vitro and in vivo. The results indicate that P110 significantly increased the DDP-induced apoptosis in SGC-7901, HCT-116, HeLa and A-549 cells. Furthermore, P110 combined with DDP significantly suppressed the growth of C26 xenograft tumors in a dose-dependent manner. This synergistic effect may be associated with DDP-induced apoptosis, involving the downregulation of Bcl-2 and the upregulation of Bax, cytochrome c and caspase-3. The results of the present study indicate that P110, in combination with chemotherapeutics, is likely to represent a potential therapeutic strategy for cancer.

Growth inhibition effect of peptide P110 plus cisplatin on various cancer cells and xenotransplanted tumors in mice