Protein-bound cisplatin could exhibit an efficient antitumor effect in vivo

Abstract

Cisplatin has been a mainstay in the treatment of various cancers, and continues to be one of the most effective and essential drugs for cancer treatment. However, the severe nephrotoxicity induced by cisplatin continues to be problematic in clinical settings. Following intravenous (i.v.) injection, cisplatin binds to serum proteins in blood circulation. Also, the contributions that protein-bound cisplatin confers to both the antitumor and adverse effects remain uncertain. In this study, therefore, we performed pharmacokinetic and pharmacological studies of protein-bound cisplatin. Following i.v. injection, protein-bound cisplatin was retained in blood circulation much longer than free-form cisplatin. The protein-bound cisplatin caused no renal toxicities, while equivalent doses of free-form cisplatin did produce this negative effect. In antitumor studies, surprisingly, sequential i.v. treatments with protein-bound cisplatin clearly suppressed tumor growth to an extent that was comparable to the same doses of free-form cisplatin both in the treatment of murine B16F10 melanoma as well as in that for human A2780 ovarian tumor-bearing mice. These results suggest that the protein-bound form partially contributes to the therapeutic outcome of i.v.-injected cisplatin for cancer treatments. Also, protein-bound cisplatin could become a novel anticancer agent to suppress tumor growth with less renal toxicity.