Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, 10000, Croatia.
J Pharm Sci. 2013 Dec;102(12):4395-405. doi: 10.1002/jps.23755. Epub 2013 Oct 17.
We investigated antitumor, genotoxic, chemopreventive, and immunostimulative effects of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse-bearing Ehrlich ascites tumor (EAT). Mice were treated with water-soluble derivative of propolis (WSDP) at a dose of 50 mg kg(-1) , 7 and 3 days before implantation of EAT cells, whereas 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. The combination of WSDP + CIS 5 mg kg(-1) at 37°C resulted in tumor growth inhibition and increased the survival of mice by additional 115.25%. WSDP with HIPEC increased the survival of mice by additional 160.3% as compared with HIPEC. WSDP reduced cisplatin toxic and genotoxic effect to normal cells without affecting cisplatin cytotoxicity on EAT cells. In addition, WSDP with HIPEC increased the cytotoxic actions of macrophages to tumor cells. Water-soluble derivative of propolis increases macrophage activity and sensitivity of tumor cells to HIPEC and reduces cisplatin toxicity to normal cells.
我们研究了局部化疗免疫治疗和高温腹腔内化疗（HIPEC）对荷 Ehrlich 腹水瘤（EAT）小鼠的抗肿瘤、遗传毒性、化学预防和免疫刺激作用。在接种 EAT 细胞前 7 天和 3 天，给小鼠注射 50mg/kg 的水溶性蜂胶衍生物（WSDP），而在接种 EAT 细胞后 3 天，将顺铂（5 或 10mg/kg）在 37°C 和 43°C 下注射。分析了以下变量：细胞总数、腹腔内细胞的差异计数、巨噬细胞的功能活性、彗星试验和微核试验。WSDP+CIS5mg/kg 在 37°C 的组合导致肿瘤生长抑制，并使小鼠的存活率额外增加 115.25%。与 HIPEC 相比，WSDP+HIPEC 使小鼠的存活率额外增加 160.3%。WSDP 降低了顺铂对正常细胞的毒性和遗传毒性，而不影响顺铂对 EAT 细胞的细胞毒性。此外，WSDP+HIPEC 增加了巨噬细胞对肿瘤细胞的细胞毒性作用。水溶性蜂胶衍生物增加了巨噬细胞的活性和肿瘤细胞对 HIPEC 的敏感性，并降低了顺铂对正常细胞的毒性。
