Therapeutic efficacy of an adenovirus-mediated anti-H-ras ribozyme in experimental bladder cancer

被引:34
作者
Irie, A
Anderegg, B
Kashani-Sabet, M
Ohkawa, T
Suzuki, T
Halks-Miller, M
Curiel, DT
Scanlon, KJ
机构
[1] Berlex Biosci, Dept Canc Res, Richmond, CA 94806 USA
[2] Univ Calif San Francisco, Mt Zion Canc Ctr, San Francisco, CA 94115 USA
[3] Berlex Biosci, Dept Pathol, Richmond, CA 94806 USA
[4] Univ Alabama Birmingham, Gene Therapy Program, Birmingham, AL 35294 USA
来源
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT | 1999年 / 9卷 / 04期
关键词
D O I
10.1089/oli.1.1999.9.341
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ras oncogenes are thought to play a critical role in cellular proliferation and tumorigenesis. Reversal of the malignant phenotype, inhibition of tumor growth, and decreased tumorgenicity have been demonstrated with the use of anti-H-ras ribozymes, In this study, the therapeutic efficacy of a hammerhead ribozyme targeting the mutated H-ras oncogene was investigated in an experimental bladder cancer model using a recombinant adenovirus as delivery vehicle. Tumors were established in nude mice by subcutaneous injection of EJ human bladder carcinoma cells harboring a point mutation of the H-ras gene. The tumors were treated with intralesional injections of an adenovirus expressing an anti-a-ras ribozyme (rAd-Hras Rz) by different schedules at serial titers, and the tumor inhibition efficacy was analyzed, The viral infection efficacy and kinetics of ribozyme expression were also evaluated, Intralesional injection of rAd-Hras Rz resulted in significant antineoplastic effects in a dose-dependent fashion. Complete regression of the tumor was achieved by rAd-Hras Rz in several cases without recurrence during the 50-day observation period. Although there was moderate vector-associated cytotoxicity in this cell line, complete regressions were not observed in the cases treated with control adenovirus vectors or vectors expressing an inactive anti-a-ras ribozyme or anti-H-ras antisense oligonucleotides, These results suggest the efficacy of a ribozyme-encoding adenovirus in the experimental gene therapy of human bladder cancer.
引用
收藏
页码:341 / 349
页数:9
相关论文
共 29 条
[1]   RAS GENES [J].
BARBACID, M .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827
[2]  
BASS C, 1995, CANCER GENE THER, V2, P97
[3]   An adenovirus mutant that replicates selectively in p53-deficient human tumor cells [J].
Bischoff, JR ;
Kim, DH ;
Williams, A ;
Heise, C ;
Horn, S ;
Muna, M ;
Ng, L ;
Nye, JA ;
SampsonJohannes, A ;
Fattaey, A ;
McCormick, F .
SCIENCE, 1996, 274 (5286) :373-376
[4]  
BOS JL, 1989, CANCER RES, V49, P4682
[5]   SPECIFIC GENE SUPPRESSION BY ENGINEERED RIBOZYMES IN MONKEY CELLS [J].
CAMERON, FH ;
JENNINGS, PA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (23) :9139-9143
[6]  
Cusack JC, 1996, CANCER GENE THER, V3, P245
[7]   Adenovirus-mediated transduction of ribozymes abrogates HER-2/neu and pleiotrophin expression and inhibits tumor cell proliferation [J].
Czubayko, F ;
Downing, SG ;
Hsieh, SS ;
Goldstein, DJ ;
Lu, PY ;
Trapnell, BC ;
Wellstein, A .
GENE THERAPY, 1997, 4 (09) :943-949
[8]  
FENG M, 1995, CANCER RES, V55, P2024
[9]   SUPPRESSION OF H-RAS-MEDIATED TRANSFORMATION IN NIH3T3 CELLS BY A RAS RIBOZYME [J].
FUNATO, T ;
SHITARA, T ;
TONE, T ;
JIAO, L ;
KASHANISABET, M ;
SCANLON, KJ .
BIOCHEMICAL PHARMACOLOGY, 1994, 48 (07) :1471-1475
[10]   TUMORIGENIC AND METASTATIC PROPERTIES OF NORMAL AND RAS-TRANSFECTED NIH/3T3 CELLS [J].
GREIG, RG ;
KOESTLER, TP ;
TRAINER, DL ;
CORWIN, SP ;
MILES, L ;
KLINE, T ;
SWEET, R ;
YOKOYAMA, S ;
POSTE, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (11) :3698-3701