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Suppression of the neoplastic phenotype in vivo by an anti-ras ribozyme
M Kashani-Sabet1, T Funato, V A Florenes
1Department of Medical Oncology, City of Hope National Medical Center, Duarte, California 91010.
Abstract:
In this study, the efficacy of an anti-ras ribozyme in reversing the neoplastic phenotype was investigated. Murine NIH3T3 cells were transfected with cellular DNA from the FEMX-I human melanoma cell line expressing the activated H-ras gene. The transformed cells displayed the neoplastic phenotype in vitro and were tumorigenic in nude mice in vivo. When the transformants were transfected by a ribozyme designed to cleave only activated H-ras RNA, the transformed phenotype was abrogated. In contrast, expression of a mutant ribozyme, essentially acting only as antisense, into the transformed cells resulted in less dramatic changes in cell growth and tumorigenicity. These results reinforce the potential role of anti-oncogene ribozymes as suppressors of neoplastic growth, with possible implications for gene therapy.
Insights
This study shows that an anti-ras ribozyme can reverse cancer cell characteristics by targeting the H-ras gene. This ribozyme therapy suppressed tumor growth, offering potential for gene therapy applications.
Area of Science:
- Molecular Biology
- Oncology
- Gene Therapy
Background:
- The H-ras gene plays a crucial role in cell proliferation and cancer development.
- Activating mutations in H-ras are common in various human cancers, including melanoma.
- Targeting oncogenes like H-ras is a promising strategy for cancer treatment.
Purpose of the Study:
- To investigate the efficacy of a specific anti-ras ribozyme in reversing the neoplastic phenotype of cancer cells.
- To evaluate the potential of ribozyme-based gene therapy for suppressing tumor growth.
Main Methods:
- Transfection of murine NIH3T3 cells with DNA from human melanoma cells expressing activated H-ras.
- Introduction of a specifically designed anti-ras ribozyme into transformed cells.
- Assessment of the ribozyme's effect on the neoplastic phenotype in vitro and tumorigenicity in vivo.
- Comparison with a mutant antisense ribozyme.
Main Results:
- The anti-ras ribozyme effectively abrogated the transformed phenotype in cancer cells.
- Tumorigenicity in nude mice was significantly reduced by the ribozyme treatment.
- A mutant antisense ribozyme showed less impact on cell growth and tumorigenicity.
Conclusions:
- Anti-ras ribozymes demonstrate significant potential as suppressors of neoplastic growth.
- These findings support the development of ribozyme-based gene therapy for oncogene-driven cancers.
- Targeted RNA cleavage by ribozymes offers a novel therapeutic approach for cancer treatment.
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