Synergism between propolis and hyperthermal intraperitoneal chemotherapy with cisplatin on Ehrlich ascites tumor in mice

Purpose: We investigated antitumor, genotoxic, chemopreventive and immunostimulative effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse bearing Ehrlich ascites tumor. Methods: Mice were treated with water soluble derivative of propolis (WSDP) at dose of 50 mg kg-1) 7 and 3 days before implantation of EAT cells, while cisplatin (5 or 10 mg kg-1) was injected 3 days after implantation of EAT cells at 37°C and 43°C. The following variables were analyzed: the total number of cells, differential count of the cells present in the peritoneal cavity, functional activity of macrophages, comet assay and micronucleus assay. Results: Combination of WSDP + CIS at 37°C resulted in tumor growth inhibition and increased the survival of mice by additional 115.25% (CIS5). WSDP with HIPEC increased survival of mice by additional 160.3% as compared with HIPEC. WSDP reduce cisplatin toxic and genotoxic effect to normal cells without effecting cisplatin cytotoxicity on EAT cells. In addition, WSDP with HIPEC increase the cytotoxic actions of macrophages to tumor cells. Conclusions: WSDP increases macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin toxicity to normal cells.