Antitumor activity of [Pt(O,O '-acac)(gamma-acac)(DMS)] in mouse xenograft model of breast cancer

作者：Muscella A^*; Vetrugno C; Migoni D; Biagioni F; Fanizzi F P; Fornai F; De Pascali S A; Marsigliante S

来源：Cell Death & Disease, 2014, 5(1): e1014.

DOI：10.1038/cddis.2013.554

• anticancer agents
• breast cancer
• pharmacokinetic
• cisplatin
• Pt(II)-analogs

The higher and selective cytotoxicity of [Pt(O, O'-acac)(gamma-acac)(DMS)] toward cancer cell in both immortalized cell lines and in breast cancer cells in primary cultures, stimulated a pre-clinical study so as to evaluate its therapeutic potential in vivo. The efficacy of [Pt(O, O'-acac)(gamma-acac)(DMS)] was assessed using a xenograft model of breast cancer developed by injection of MCF-7 cells in the flank of BALB/c nude mice. Treatment of solid tumor-bearing mice with [Pt(O, O'-acac)(gamma-acac)(DMS)] induced up to 50% reduction of tumor mass compared with an average 10% inhibition recorded in cisplatin-treated animals. Thus, chemotherapy with [Pt(O, O'-acac)(gamma-acac)(DMS)] was much more effective than cisplatin. We also demonstrated enhanced in vivo pharmacokinetics, biodistribution and tolerability of [Pt(O, O'-acac)(gamma-acac)(DMS)] when compared with cisplatin administered in Wistar rats. Pharmacokinetics studies with [Pt(O, O'-acac)(gamma-acac)(DMS)] revealed prolonged Pt persistence in systemic blood circulation and decreased nefrotoxicity and hepatotoxicity, major target sites of cisplatin toxicity. Overall, [Pt(O, O'-acac)(gamma-acac)(DMS)] turned out to be extremely promising in terms of greater in vivo anticancer activity, reduced nephrotoxicity and acute toxicity compared with cisplatin.

• 出版日期2014-1