一种溶瘤腺病毒抑制肿瘤细胞的作用机制及特异性研究  

Study on the mechanism and specificity of an oncolytic adenovirus(recombinant human adenovirus type 5)inhibiting the proliferation of tumor cells

作　　者：琚姝 王爱霞 JU Shu;WANG Aixia(Shanghai Sunway Biotech Co.,Ltd.,Shanghai 201206,China)

机构地区：[1]上海三维生物技术有限公司,上海201206

出　　处：《上海医药》2024年第15期65-68,共4页Shanghai Medical & Pharmaceutical Journal

摘　　要：研究重组人5型腺病毒(H101)抑制肿瘤细胞增殖的作用机制及特异性。采用体外细胞培养方法及TCID_(50)检测病毒滴度法,发现H101对p53^(−)的肿瘤细胞有显著的选择性复制作用,其活性可以对p53突变的肿瘤组织产生溶瘤作用从而达到治疗效果;采用体外药效学实验检测H101对10种肿瘤细胞株的抑增殖作用,通过计算IC_(50)、IC_(90)进一步得出小鼠肝癌细胞Hepa1-6、小鼠胰腺癌细胞Pan02、小鼠神经胶质瘤细胞GL261对H101较为敏感。研究结果表明H101对已获批的适应证之外的其他肿瘤细胞也有溶瘤作用,具有适应证扩展的潜力。本研究可为后续开展动物模型的体内药效实验和使用剂量的选择提供参考。The mechanism and specificity of human adenovirus type 5(H101)in inhibiting tumor cells were studied.By in vitro cell culturation and TCID_(50) virus titer test,it was found that the oncolytic adenovirus had a significant selective replication effect on p53^(-)tumor cells and its replication ability could produce oncolytic effect on p53 mutated tumor tissue and achieved therapeutic effect.In vitro pharmacodynamic experiment was used to detect the inhibitory effect of H101 on ten tumor cell lines.By calculating IC_(50) and IC_(90),it was further concluded that H101 was sensitive to the mouse hepatoma cell Hepa1-6,the mouse pancreatic cancer cell Pan02 and the mouse glioma cell GL261.These results showed that H101 had oncolytic effects on other tumor cells beyond the approved indications and a potential for expanding indications.This study can also provide reference for the selection of animal models and dosage for subsequent in vivo pharmacological experiments.

关 键 词：溶瘤腺病毒 肿瘤治疗 体外药效学 增殖抑制 

分 类 号：R979.19[医药卫生—药品] R730.54[医药卫生—药学]