树舌灵芝多糖温敏凝胶联合紫杉醇抗4T1小鼠乳腺癌研究  

Thermosensitive gel of polysaccharide from Ganoderma applanatum combined with paclitaxel for mice with 4T1 breast cancer

作　　者：唐岚[1] 朱转凤 曹李鹏 沈淼 高炎 屠超杰 张振海[2] 单伟光[1] TANG Lan;ZHU Zhuan-feng;CAO Li-peng;SHEN Miao;GAO Yan;TU Chao-jie;ZHANG Zhen-hai;SHAN Wei-guang(College of Pharmacy,Zhejiang University of Technology,Hangzhou 310014,China;Key Laboratory of New Drug Delivery System of Chinese Materia Medica,Jiangsu Provincial Academy of Chinese Medicine,Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,China)

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]南京中医药大学附属中西医结合医院江苏省中医药研究院国家中医药管理局中药释药系统重点研究室,江苏南京210028

出　　处：《中国中药杂志》2020年第11期2533-2539,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81403117)。

摘　　要：树舌灵芝多糖具有抗癌和增强免疫功能的作用,其瘤内注射抗肿瘤未见报道。该研究采用水提醇沉法从树舌灵芝中提取多糖,经Sevage法除蛋白,陶瓷膜纯化,获得总糖量约为63%的树舌多糖。树舌多糖和紫杉醇联用,在较低浓度时,对4T1细胞的体外细胞毒活性有协同作用。此外,4T1细胞的生长曲线显示,树舌多糖能逐渐延缓4T1细胞的生长。采用泊洛沙姆188和407为基质制备了树舌多糖温敏凝胶,胶凝温度为36℃,温敏凝胶能有效地减缓树舌多糖体外释放速率。以4T1乳腺癌荷瘤小鼠为模型,考察了树舌多糖温敏凝胶瘤内注射联用紫杉醇(白蛋白结合型)尾静脉注射的治疗效果,高、低剂量树舌多糖温敏凝胶组每只小鼠分别瘤内给予树舌多糖2.25,1.125 mg,给药2次,紫杉醇剂量为15 mg·kg-1,每3 d给药1次,给药5次。树舌多糖温敏凝胶高剂量组的抑瘤率为29.65%,紫杉醇组的抑瘤率为58.58%,低、高剂量树舌多糖温敏凝胶与紫杉醇联合用药组抑瘤率分别为63.37%,68.10%。高剂量树舌多糖温敏凝胶与紫杉醇联用对肿瘤的抑制效果较紫杉醇组显著增强(P<0.05)。研究结果显示,使用紫杉醇治疗时,联合应用树舌多糖温敏凝胶瘤内注射,可以提高4T1小鼠乳腺癌的治疗效果,降低化疗副作用。Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function.There were no reports on antitumor effect of its intratumoral injection.In this study,the polysaccharide was extracted from G.applanatum by water extraction and alcohol precipitation,and purified by ceramic membrane after removing protein by Sevage method.The total polysaccharide content from G.applanatum(PGA)was about 63%.The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro.In addition,the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually.The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407.The gel temperature was 36℃,and the PGA-TG could effectively slow down the release rate of PGA in vitro.4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX).In high and low dose PGA groups,each mice was given with 2.25,1.125 mg PGA respectively,twice in total,and the dosage of paclitaxel was 15 mg·kg-1,once every 3 days,for a total of five times.The tumor inhibition rate was 29.65%in the high dose PGA-TG group,58.58%in the nab-PTX group,63.37%in low dose PGA-TG combined with nab-PTX group,and 68.10%in high dose PGA-TG combined with nab-PTX group respectively.The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05).The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.

关 键 词：树舌多糖 温敏凝胶 紫杉醇 乳腺癌 联合治疗 

分 类 号：R737.9[医药卫生—肿瘤]