A mechanism of cisplatin action: antineoplastic effect through inhibition of neovascularization

Though cisplatin (cis-diamminedichloroplatinum; CDDP) has been widely used for the treatment of malignant tumors, the mechanism of its action has not been well understood. Neovascularization, which accompanies tumor growth and metastasis, is required for cell proliferation in order to supply both oxygen and nutrients. We have studied in this investigation the effect of CDDP on endothelial cell (EC) proliferation in vitro and on rabbit corneal neovascularization in vivo. DNA synthesis of human umbilical EC was inhibited by CDDP in a dose-dependent fashion. Significant inhibition was observed at concentration over 10(-8) M, which is attainable in the serum of treated patients. Rabbit corneal neovascularization in vivo was also suppressed by intravenous injection of 0.5 mg/kg of CDDP for 10 days. These results suggest that CDDP might have an indirect anti-neoplastic effect through the suppression of neovascularization required for the tumor growth.