Zhou Jian-Feng, Chen Gang, Lu Yun-Ping, Wang Shi-Xuan, Ma Ding
Cancer Molecular Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Ai Zheng. 2003 Dec;22(12):1264-7.
BACKGROUND & OBJECTIVE: Adenovirus vector-mediated herpes simplex virus thymidine kinase gene (ADV-TK) transfer is one of the major gene therapy strategies for tumor. This study was designed to determine the in vitro anti-tumor efficiency of ADV-TK, a recombinant construct previously developed in our laboratory.
Herpes simplex virus thymidine kinase (TK) gene was transduced into 14 types of cultured tumor cells with different histological origins using adenovirus vector followed by ganciclovir (GCV) medication. The killing efficiency was measured using MTT assay.
At the dosage of 1x10(9) viral particles/per well in the presence of 100 microg/ml GCV, ADV-TK/GCV caused effective killing of 11 out of total 14 types of tumor cells with a rate higher than 74%, the other 3 tumor cells, laryngeal epithelial cancer cells (Hep-2), hepatic cancer cells (Bel7402), and human colon cancer cells (HCT-8) were less sensitive to the ADV-TK/GCV treatment with the killing rates of 55.3%+/-2.0%, 61.3%+/-2.0%, and 63.7%+/-2.5%, respectively. Except for Hep-2, the killing efficiency caused by ADV-TK/GCV treatment was similar to that caused by cisplatin at a dosage equal to the in vivo peak concentration (5 microg/ml) in tissue.
ADV-TK is highly efficient for active killing of tumor cells in vitro and is promising for future clinical application.
腺病毒载体介导的单纯疱疹病毒胸苷激酶基因(ADV-TK)转移是肿瘤主要的基因治疗策略之一。本研究旨在确定我们实验室之前构建的重组体ADV-TK的体外抗肿瘤效率。
利用腺病毒载体将单纯疱疹病毒胸苷激酶(TK)基因转导至14种具有不同组织学来源的培养肿瘤细胞中,随后给予更昔洛韦(GCV)处理。采用MTT法测定杀伤效率。
在100μg/ml GCV存在的情况下,以1×10⁹病毒颗粒/孔的剂量,ADV-TK/GCV有效杀伤了14种肿瘤细胞中的11种,杀伤率高于74%,另外3种肿瘤细胞,即喉上皮癌细胞(Hep-2)、肝癌细胞(Bel7402)和人结肠癌细胞(HCT-8)对ADV-TK/GCV处理的敏感性较低,杀伤率分别为55.3%±2.0%、61.3%±2.0%和63.7%±2.5%。除Hep-2外,ADV-TK/GCV处理引起的杀伤效率与顺铂在组织中等于体内峰值浓度(5μg/ml)的剂量下所引起的杀伤效率相似。
ADV-TK在体外对肿瘤细胞具有高效的主动杀伤作用,具有良好的临床应用前景。