Suzuki Ikukatsu, Hayashi Ikuo, Takaki Takayuki, Groveman Debra S, Fujimiya Yoshiaki
Department of Clinical Nutrition, Faculty of Health Sciences, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan.
Cancer Biother Radiopharm. 2002 Oct;17(5):553-62. doi: 10.1089/108497802760804781.
Using an ICR mouse model bearing a syngeneic Ehrlich ascitis carcinoma, the present study was undertaken to examine the effects of crude, water-soluble propolis (CWSP) on tumor progression, chemotherapeutic efficacy, and hematopoiesis in the peripheral blood. It was demonstrated that CWSP, administered subcutaneously, resulted in marked regression of tumor growth in mice, at the early phase after tumor inoculation (CWSP, p < 0.05 vs. saline control). Molecular analysis indicated that the CWSP is composed of 8.4% protein, 4.2% quercetin plus a variety of saccharides with a molecular weight of 29 kDa. Orally administered CWSP did not produce any regression for the observation period (oral CWSP, p > 0.05 vs. saline control). Peritoneal injection of CWSP into neonatal mice resulted in an increased lymphocyte/polymorphonuclear leukocyte ratio activity, indicating the potential activation of lymphoid cell lineages. These observations suggest that subcutaneously injected CWSP could regulate the development of tumors by possibly stimulating multicellular immunity. In addition, oral administration of CWSP concurrently with 5-fluorouracil (5-FU) or mitomycin C (MMC), significantly increased tumor regression as compared with the respective chemotherapy alone, illustrating the adjuvant effect of orally administered CWSP for tumor regression when combined with chemotherapeutic agents. To examine further the potential usefulness of CWSP for chemotherapeutic regimens, which induce profound multilineage hematopoietic suppression, mice that received CWSP orally in addition to a 5-FU or MMC were followed for absolute numbers of platelets and white and red blood cells. The oral administration of CWSP significantly ameliorated the cytopenia induced by 5-FU, resulting in recovery of white as well as red blood cell counts (5-FU plus CWSP, p < 0.05 vs. 5-FU alone or water control; white blood cells on day 15, red blood cells on day 25), but no marked effects on platelet counts was observed (5-FU plus CWSP, p > 0.05 vs. 5-FU alone or water control). On the other hand, CWSP significantly reduced all three MMC-induced cytopenias, especially at the later stage of the chemotherapeutic course (after day 30), suggesting repetitive requirements of oral administration of CWSP. In summary, subcutaneous administration of an aqueous CWSP resulted in marked regression of transplanted tumors. Orally administered CWSP combined with chemotherapeutic agents significantly increased tumor regression and ameliorated the cytopenia induced by the chemotherapeutic agents alone. These results suggest the benefits of potential clinical trials using CWSP combined with chemotherapeutic agents in order to maximize enhanced immunity while potentially minimizing postchemotherapeutic deteriorated reactions.
本研究采用携带同基因艾氏腹水癌的ICR小鼠模型，旨在探讨粗制水溶性蜂胶（CWSP）对肿瘤进展、化疗疗效及外周血造血功能的影响。结果表明，在肿瘤接种后的早期阶段，皮下注射CWSP可使小鼠肿瘤生长显著消退（CWSP组与生理盐水对照组相比，p < 0.05）。分子分析表明，CWSP由8.4%的蛋白质、4.2%的槲皮素以及多种分子量为29 kDa的糖类组成。在观察期内，口服CWSP未产生任何肿瘤消退作用（口服CWSP组与生理盐水对照组相比，p > 0.05）。向新生小鼠腹腔注射CWSP可使淋巴细胞/多形核白细胞比率活性增加，表明淋巴样细胞系有潜在激活。这些观察结果提示，皮下注射CWSP可能通过刺激多细胞免疫来调节肿瘤的发展。此外，与单独化疗相比，口服CWSP与5-氟尿嘧啶（5-FU）或丝裂霉素C（MMC）同时给药可显著增加肿瘤消退，说明口服CWSP与化疗药物联合使用时对肿瘤消退具有辅助作用。为进一步研究CWSP在诱导严重多系造血抑制的化疗方案中的潜在用途，对除接受5-FU或MMC外还口服CWSP的小鼠的血小板、白细胞和红细胞绝对数量进行了跟踪。口服CWSP可显著改善5-FU诱导的血细胞减少，使白细胞和红细胞计数恢复（5-FU加CWSP组与单独5-FU组或水对照组相比，p < 0.05；第15天的白细胞，第25天的红细胞），但对血小板计数未观察到明显影响（5-FU加CWSP组与单独5-FU组或水对照组相比，p > 0.05）。另一方面，CWSP可显著减轻MMC诱导的所有三种血细胞减少，尤其是在化疗疗程后期（第30天后），提示需要重复口服CWSP。总之，皮下注射水性CWSP可使移植肿瘤显著消退。口服CWSP与化疗药物联合使用可显著增加肿瘤消退，并改善单独化疗药物诱导的血细胞减少。这些结果表明，进行CWSP与化疗药物联合使用的潜在临床试验可能有益，以便在可能最小化化疗后不良反应的同时最大化增强免疫力。
