抗EGFR、CA199及MUC1单克隆抗体偶联吉西他滨聚氰基丙烯酸正丁酯纳米粒杀伤胰腺癌细胞作用的比较研究  

The Comparative Study on the Inhibitory Effect of Gemcitabine Polybutylcyanoacrylate Anoparticles Coupled with EGFR,CA199 and MUC1 Monoclonal Antibodies on Pancreatic Cancer Cells

作　　者：张林 侯艳红 李春梅 刘浩润 Zhang Lin;Hou Yanhong;Li Chunmei(Department of Gastroenterology,8th Medical Center,PLA General Hospital,Beijing 100091,China)

机构地区：[1]中国人民解放军总医院第八医学中心消化内科,北京100091

出　　处：《四川医学》2020年第11期1121-1126,共6页Sichuan Medical Journal

摘　　要：目的比较抗人EGFR、CA199和MUC1三种单克隆抗体分别偶联的载药聚氰基丙烯酸正丁酯纳米颗粒对人胰腺癌细胞的体外杀伤作用,进一步筛选靶向效果更佳的目标分子。方法采用乳化聚合法制备负载吉西他滨的纳米微球,测定载药纳米粒的粒径、载药率、包封率。采用化学交联法分别制备抗EGFR、CA199和MUC1三种单克隆抗体偶联的载吉西他滨聚氰基丙烯酸正丁酯纳米微球(EGFR-GEM-PBCA-NP、CA199-GEM-PBCA-NP、MUC1-GEM-PBCA-NP)。进行三种纳米粒子杀伤胰腺癌靶细胞实验,MTT比色法杀伤实验检测,并设置单纯负载吉西他滨的纳米微球、吉西他滨原料药及空白对照组,比较三种单抗修饰的靶向纳米粒对胰腺癌细胞的杀伤能力。使用流式细胞仪法检测治疗后肿瘤细胞周期与凋亡情况变化。结果与对照组相比各实验组的细胞杀伤率差异有统计学意义(P<0.05),其中MUC1-GEM-PBCA-NP组显著高于其他各组。MUC1-GEM-PBCA-NP处理组细胞凋亡率显著高于其他各组(P<0.05)。结论在体外实验中MUC1修饰的载药纳米粒子对人胰腺癌细胞的靶向抑制及杀伤作用优于EGFR单抗及CA199单抗修饰的载药纳米粒子,其对于体外培养细胞的再导向作用更强。Objective To compare the killing effect of drug loading polybutylcyanoacrylate particles coupled with human EGFR,CA199 and MUC1 monoclonal antibodies on human pancreatic cancer cells in vitro,and to screen the more effective targeted molecule for the clinical treatment of pancreatic cancer with this method.Methods To prepare gemcitabine loaded nanocrystalline microspheres by emulsion polymerization,and to determine the size,drug loading rate and encapsulation rate of drug loading nanocrystalline nanoparticles.Gemcitabine polybutylcyanoacrylate coupled with EGFR,CA199 and MUC1 monoclonal antibodies(EGFR-GEM-PBCA-NP,CA199-GEM-PBCA-NP,MUC1-GEM-PBCA-NP)were prepared by chemical crosslinking method to kill pancreatic cancer cells.The cell killing rates were detected by MTT assay.The changes of tumor cell cycle and apoptosis after treatment were detected by flow cytometry.Results Compared with the control group,the cell killing rate of each experimental group was significantly different(P<0.05),among which the MUC1-GEM-PBCA-NP group was significantly higher than the other groups(P<0.05).The apoptosis rate of MUC1-GEM-PBCA-NP treatment group was significantly higher than those of other groups(P<0.05).Conclusion In vitro,MUC1-GEM-PBCA-NP can inhibit and kill human pancreatic cancer cells more effectively than EGFR-GEM-PBCA-NP or CA199-GEM-PBCA-NP.MUC1 could be the best targeted molecule in these three molecules.

关 键 词：胰腺癌 纳米微粒 CA199 EGFR MUC1 靶向治疗 

分 类 号：R573.3[医药卫生—消化系统]