Replication-selective Oncolytic Adenovirus CNHK300 in the Treatment of Breast Cancer Cell Lines in vitro  

肿瘤选择性增殖腺病毒CNHK300治疗乳腺癌的体外实验研究(英文)

作　　者：李月敏[1] 宋三泰[1] 江泽飞[1] 徐建明[1] 张琪[1] 钱其军 

机构地区：[1]北京军事医学科学院附属307医院乳癌内科,100071

出　　处：《The Chinese-German Journal of Clinical Oncology》2005年第6期334-337,共4页中德临床肿瘤学杂志（英文版）

基　　金：This work was supported by International Cooperation Important Project of National Natural Sciences Foundation of China(No. 30120160824) and the State 863 High Technology R&D Project of China (No. 2001AA217031)

摘　　要：Objective： To evaluate the tumor selectivity and therapeutic efficiency of replication-competent adenovirus CNHK300 on human breast cancer cells. Methods： RT-PCR was used to detect the hTERT mRNA activity in various breast cancer and normal fibroblast cell lines. Virus proliferation assay, cell viability assay and Western blot were applied to evaluate the proliferation and cytolysis selectivity of CNHK300. Results： The telomerase activity of MCF-7, BT-549 and SK-BR-3 was positive, while telomerase in MRC-5 and BJ was negative. The progeny virus titers in MCF-7, BT-549 and SK-BR-3 after 48 h of CNHK300 exposure was 40 625, 1 265 and 20 000 fold higher than those of 0 h, even slightly higher than those of wtAd5 （except in SK-BR-3）. ONYX-015 virus proliferation ability was weaker than that of CNHK300 in cancer cells. However, CNHK300 exhibited attenuated replicative ability as compared with wtAd5 in MRC-5 and BJ. The CNHK300 replicatative multiple was 63 and 192 fold at 48 h respectively, while the wtAd5 still multiplied 3 160-4 846 fold. CNHK300 could cause about half of breast cancer cells to die within 7 days at MOI 10 pfu/cell and below, whereas the IC50 in BJ and MRC-5 was as high as MOI 100 pfu/cell. CNHK300 E1A protein could be detected in breast cancer cells and 293 cells but not in normal fibroblast cells. Conclusion： hTERT promoter can successfully modulate the CNHK300 to be selectively replicated in breast cancer cells positive for telomerase, which may be a potential treatment strategy in breast cancer.

关 键 词：gene therapy VIROTHERAPY replicative adenovirus breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]