Greco O, Folkes L K, Wardman P, Tozer G M, Dachs G U
Gray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex, UK.
Cancer Gene Ther. 2000 Nov;7(11):1414-20. doi: 10.1038/sj.cgt.7700258.
This paper demonstrates the potential for utilizing the plant enzyme, horseradish peroxidase (HRP), in a gene-directed enzyme prodrug therapy context. Human T24 bladder carcinoma cells transfected with a mammalian expression vector containing the HRP cDNA were selectively sensitized to the nontoxic plant hormone, indole-3-acetic acid (IAA). The HRP/IAA-induced cell kill was effective in normoxic and anoxic conditions. The activated drug is a long-lived species able to cross cell membranes, and cell contact appears not to be required for a bystander effect to take place. These preliminary results suggest that the delivery of the HRP gene to human tumors followed by IAA treatment may provide a novel cancer gene-directed enzyme prodrug therapy approach, with potential to target hypoxic cells.
本文证明了在基因导向酶前药疗法的背景下利用植物酶辣根过氧化物酶（HRP）的潜力。用含有HRP cDNA的哺乳动物表达载体转染的人T24膀胱癌细胞对无毒植物激素吲哚-3-乙酸（IAA）具有选择性敏感性。HRP/IAA诱导的细胞杀伤在常氧和缺氧条件下均有效。活化的药物是一种能够穿过细胞膜的长寿物质，旁观者效应的发生似乎不需要细胞接触。这些初步结果表明，将HRP基因导入人类肿瘤后再进行IAA治疗可能提供一种新型的癌症基因导向酶前药疗法，具有靶向缺氧细胞的潜力。
