Suzuki T, Anderegg B, Ohkawa T, Irie A, Engebraaten O, Halks-Miller M, Holm P S, Curiel D T, Kashani-Sabet M, Scanlon K J
Cancer Research Department, Berlex Biosciences, Richmond, CA, USA.
Gene Ther. 2000 Feb;7(3):241-8. doi: 10.1038/sj.gt.3301065.
HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared an anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high efficiency, resulting in decreased HER-2/neu expression. In vivo injections of rAdHER-Rz into BT-474 tumors established in nude mice inhibited tumor growth to 20% of mock-treated controls. Similar in vivo effects were shown in MCF-7 cells, which do not overexpress HER-2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector. These results suggest the utility of anti-HER-2/neu ribozymes as a rational strategy for gene therapy of breast cancer. Gene Therapy (2000) 7, 241-248.
HER-2/neu在25%至30%的人类乳腺癌中过度表达。我们制备了一种由重组腺病毒(rAdHER-Rz)表达的抗HER-2/neu锤头状核酶。人乳腺癌细胞系被高效转导,导致HER-2/neu表达降低。向裸鼠体内建立的BT-474肿瘤注射rAdHER-Rz可将肿瘤生长抑制至模拟处理对照组的20%。在未过度表达HER-2/neu的MCF-7细胞中也显示出类似的体内效应。rAdHER-Rz的生长抑制作用大于反义表达载体。这些结果表明抗HER-2/neu核酶作为乳腺癌基因治疗的合理策略具有实用性。《基因治疗》(2000年)7卷,241 - 248页。