Moon Seong-Hoon, Heo Jin-Chul, Fine Robert L, Kim Hwan-Mook, Kim Sung-Uk, Yoon Byung-Dae, Lee Sang-Han
Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon 305-333, Korea.
Int J Oncol. 2005 Feb;26(2):395-404.
We carried out in vitro and in vivo assays to investigate the immunomodulatory and immunochemotherapeutic action mechanism of BRD-glucan, a high molecular weight ( approximately 3,500 kDa) polysaccharide isolated from Aureobasidium sp, and assessed the efficacy of BRD-glucan/adriamycin co-treatment of animal cancer models. RT-PCR and suspension hemolytic, plaque forming, wounding, invasion and cell proliferation assays were utilized to investigate the in vitro immunochemotherapeutic effects of BRD-glucan. In vivo, the effects of BRD-glucan and BRD-glucan/adriamycin co-treatment were tested in a B16 melanoma initiation model and in C57BL/6 mice. In vitro, BRD-glucan did not affect the cellular wounding response or invasion activity; treatment with BRD-glucan led to increase proliferation of B cells, natural killer cells and macrophages, but not T cells. In addition, we found that the BRD-glucan activation of B cells and macrophages was dependent on Toll-like receptor2 (TLR2) and TLR4, which play important roles in innate and adaptive immunity. In vivo, BRD-glucan/adriamycin co-treatment effectively reduced the number and size of metastatic colonies. Based on the results of our in vitro and in vivo toxicity, safety and immunochemotherapy assays, we propose that BRD-glucan is a promising immunochemotherapeutic anti-tumor agent.
我们进行了体外和体内试验，以研究从出芽短梗霉中分离出的一种高分子量（约3500 kDa）多糖BRD-葡聚糖的免疫调节和免疫化学治疗作用机制，并评估了BRD-葡聚糖/阿霉素联合治疗动物癌症模型的疗效。利用逆转录聚合酶链反应（RT-PCR）以及悬浮溶血、空斑形成、创伤、侵袭和细胞增殖试验来研究BRD-葡聚糖的体外免疫化学治疗效果。在体内，在B16黑色素瘤起始模型和C57BL/6小鼠中测试了BRD-葡聚糖和BRD-葡聚糖/阿霉素联合治疗的效果。在体外，BRD-葡聚糖不影响细胞创伤反应或侵袭活性；用BRD-葡聚糖处理导致B细胞、自然杀伤细胞和巨噬细胞增殖增加，但不影响T细胞。此外，我们发现BRD-葡聚糖对B细胞和巨噬细胞的激活依赖于Toll样受体2（TLR2）和TLR4，它们在先天免疫和适应性免疫中起重要作用。在体内，BRD-葡聚糖/阿霉素联合治疗有效减少了转移瘤集落的数量和大小。基于我们体外和体内毒性、安全性及免疫化学治疗试验的结果，我们提出BRD-葡聚糖是一种有前景的免疫化学治疗抗肿瘤药物。
