Di.S.Te.B.A., University of Salento, Lecce, Italy.
I.R.C.C.S. Neuromed, Pozzilli, Italy.
Cell Death Dis. 2014 Jan 23;5(1):e1014. doi: 10.1038/cddis.2013.554.
The higher and selective cytotoxicity of [Pt(O,O'-acac)(γ-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)(γ-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)(γ-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)(γ-acac)(DMS)] was much more effective than cisplatin. We also demonstrated enhanced in vivo pharmacokinetics, biodistribution and tolerability of [Pt(O,O'-acac)(γ-acac)(DMS)] when compared with cisplatin administered in Wistar rats. Pharmacokinetics studies with [Pt(O,O'-acac)(γ-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)(γ-acac)(DMS)] turned out to be extremely promising in terms of greater in vivo anticancer activity, reduced nephrotoxicity and acute toxicity compared with cisplatin.
[Pt(O,O'-acac)(γ-acac)(DMS)]对永生化细胞系和原代乳腺癌细胞中的癌细胞具有更高和选择性的细胞毒性，这激发了一项临床前研究，以评估其在体内的治疗潜力。通过将 MCF-7 细胞注射到 BALB/c 裸鼠的侧腹来建立乳腺癌的异种移植模型，来评估 [Pt(O,O'-acac)(γ-acac)(DMS)]的疗效。与顺铂治疗的动物平均抑制 10%相比，用 [Pt(O,O'-acac)(γ-acac)(DMS)]治疗实体瘤荷瘤小鼠可使肿瘤质量减少高达 50%。因此，与顺铂相比，[Pt(O,O'-acac)(γ-acac)(DMS)]的化疗更有效。与顺铂在 Wistar 大鼠中的给药相比，我们还证明了 [Pt(O,O'-acac)(γ-acac)(DMS)]的体内药代动力学、生物分布和耐受性得到了增强。[Pt(O,O'-acac)(γ-acac)(DMS)]的药代动力学研究表明，其在全身血液循环中的 Pt 持续时间延长，并且肾毒性和肝毒性降低，这是顺铂毒性的主要靶位。总的来说，与顺铂相比，[Pt(O,O'-acac)(γ-acac)(DMS)]在体内抗癌活性更高、肾毒性和急性毒性降低方面极具潜力。
