Shin Han Jae, Kim Young Sook, Kwak Yi Seong, Song Yong Bum, Kim Young Sang, Park Jong Dae
KT&G Central Research Institute, Daejeon, Korea.
Planta Med. 2004 Nov;70(11):1033-8. doi: 10.1055/s-2004-832643.
We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C.A. Meyer), shows immunomodulatory and antitumor activities, mainly mediated by the nitric oxide (NO) production of macrophages. This compound may be used in cancer therapy alone or in combination with other chemotherapeutic agents. The synergistic effect of RGAP and paclitaxel (taxol) was evaluated to develop new biological response modifiers in cancer therapy. The present study demonstrates a synergistic antitumor effect of RGAP and paclitaxel in mice transplanted with sarcoma 180 and B16 melanoma. Combined treatment with paclitaxel (5 or 15 mg/kg) and RGAP (25 mg/kg) resulted in a 28.6 or 42.8 % increase in the life span of ICR mice bearing sarcoma 180 tumor cells, while no obvious effect was seen on sole paclitaxel treatment. When a combination of paclitaxel (10 mg/kg) and RGAP (100 mg/kg) was administered to C57BL/6 mice implanted with B16 melanoma, the tumor weight per mouse also decreased by 76.3 %, suggesting that RGAP may be used as an adjuvant in medicinal applications of paclitaxel. The augmented antitumor effect of paclitaxel is supposed to be the result of the immunomodulating antitumor effect of RGAP. RGAP, having B cell specific mitogenic activity, induced the secretion of interleukin-6 (IL-6) in spleen cells in a concentration-dependent manner (5 to 500 microg/microL). RGAP also restored the proliferation of splenocytes and NK cell activity suppressed by paclitaxel. Flow cytometric analysis of splenocytes in mice treated with paclitaxel showed a significant increase of CD11b+ cells. Additionally, a synergistic effect of RGAP and paclitaxel was found to effect an increased tumoricidal activity of macrophages. The above results suggest that clinical trials of RGAP as an adjuvant in cancer chemotherapy of paclitaxel are highly feasible.
我们最近报道，从高丽红参（Panax ginseng C.A. Meyer）中分离得到的红参酸性多糖（RGAP）具有免疫调节和抗肿瘤活性，主要通过巨噬细胞产生一氧化氮（NO）介导。该化合物可单独用于癌症治疗，或与其他化疗药物联合使用。为了开发癌症治疗中的新型生物反应调节剂，评估了RGAP与紫杉醇（泰素）的协同作用。本研究证明了RGAP和紫杉醇在移植有肉瘤180和B16黑色素瘤的小鼠中具有协同抗肿瘤作用。紫杉醇（5或15 mg/kg）与RGAP（25 mg/kg）联合治疗使携带肉瘤180肿瘤细胞的ICR小鼠寿命分别延长了28.6%或42.8%，而单独使用紫杉醇治疗未见明显效果。当将紫杉醇（10 mg/kg）与RGAP（100 mg/kg）联合给予植入B16黑色素瘤的C57BL/6小鼠时，每只小鼠的肿瘤重量也减少了76.3%，这表明RGAP可作为紫杉醇药物应用中的佐剂。紫杉醇增强的抗肿瘤作用被认为是RGAP免疫调节抗肿瘤作用的结果。具有B细胞特异性促有丝分裂活性的RGAP以浓度依赖方式（5至500 μg/μL）诱导脾细胞分泌白细胞介素-6（IL-6）。RGAP还恢复了被紫杉醇抑制的脾细胞增殖和NK细胞活性。对用紫杉醇治疗的小鼠脾细胞进行流式细胞术分析显示CD11b+细胞显著增加。此外，发现RGAP和紫杉醇的协同作用可提高巨噬细胞的杀肿瘤活性。上述结果表明，RGAP作为紫杉醇癌症化疗佐剂的临床试验具有很高的可行性。
