分子靶向药物索拉非尼微晶制剂的制备及其裸鼠体内抗肿瘤活性研究  

In Vivo Anti-Tumor Efficiency of Sorafenib-Microcrystal Agents on Hepatocellular Carcinoma Cells

作　　者：蒋征奎 李晓[2,3] 王学方[2,3] JIANG Zheng-kui;LI Xiao;WANG Xue-fang(The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, China;Henan Academy of Sciences, Zhengzhou 450002, China;Biological Developing Center, Henan Academy of Sci- ences, Zhengzhou 450002, China)

机构地区：[1]郑州大学附属肿瘤医院(河南省肿瘤医院),郑州450000 [2]河南省科学院,郑州450002 [3]河南省生物技术开发中心,郑州450002

出　　处：《中国药学杂志》2018年第11期906-911,共6页Chinese Pharmaceutical Journal

摘　　要：目的制备分子靶向药物索拉非尼(sorafenib)的微晶制剂,确定其在体内的缓释性质与是否具有对肝细胞癌(hepatocellular carcinoma,HCC)的长效抗肿瘤活性。方法制备索拉非尼的增溶制剂与微晶制剂,建立HCC细胞MHCC97-H的皮下肿瘤模型,在MHCC97-H细胞皮下肿瘤中分别注射索拉非尼的增溶制剂或微晶制剂,在系列时间点留取实验动物的血液或肿瘤组织标本,通过检测血液与肿瘤标本中索拉非尼的含量确定微晶制剂是否具有缓释特性。进一步,在皮下肿瘤组织中分别注射索拉非尼的增溶制剂或微晶制剂,检测肿瘤组织在免疫缺陷小鼠皮下的生长情况。以定量PCR(qPCR)检测皮下肿瘤中上皮间质转化(epithelial-mesenchymal transition,EMT)相关指示分子的mRNA表达。从皮下肿瘤组织表面剥取性状良好的组织微块,移植于免疫缺陷小鼠肝脏,检测不同组皮下肿瘤中HCC细胞在肝脏原位的生长情况。结果与索拉非尼增溶制剂相比,索拉非尼微晶制剂具有缓释特性。单次给予索拉非尼微晶制剂能够实现对HCC皮下肿瘤的抑制作用。结论制备得到分子靶向药物索拉非尼微晶制剂,其具明确的抗肿瘤活性。OBJECTIVE To obtain the microcrystal agents of sorafenib and examine the in vivo anti-tumor efficiency of sorafenibmicrocrystal on hepatocellular carcinoma cells. METHODS The solubilizing solution or microcrystal of sorafenib was obtained. A highly aggressive HCC cell line, MHCC97-H, was used to form the subcutaneous or intra-hepatic tumor model in nude mice. Sorafenib-solution or microcrystal was injected into tumors. The clearance curve or anti-tumor efficiency of solubilizing solution or microcrystal was identified. Endogenous of EMT related indicators was identified by qPCR. RESULTS Sorafenib slowly released in tumor tissues by sorafenib-microcrystal but not sorafenib-solution. Treatment of sorafenib-microcrystal inhibited the in vivo growth of MHCC97- H cells. CONCLUSION The microcrystal agents of sorafenib is prepared. This work also establishes the in vivo anti-tumor efficiency of sorafenib-microcrystal on HCC ceils.

关 键 词：肝细胞癌 索拉非尼 药物微晶制剂 

分 类 号：R817.1[医药卫生—影像医学与核医学] R735.7[医药卫生—放射医学]