siRNA Knockdown of Ribonucleotide Reductase Inhibits Melanoma Cell Line Proliferation Alone or Synergistically with Temozolomide
| Autor: | Teli Hsueh, Mark E. Davis, Jonathan E. Zuckerman, Richard C. Koya, Antoni Ribas |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Small interfering RNA
Cell cycle checkpoint Skin Neoplasms Ribonucleoside Diphosphate Reductase Dermatology Biology Biochemistry S Phase 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Temozolomide Humans Gene Silencing RNA Small Interfering Antineoplastic Agents Alkylating Melanoma Molecular Biology 030304 developmental biology Cell Proliferation 0303 health sciences Gene knockdown Cell growth Cell Cycle G1 Phase Cell Biology medicine.disease 3. Good health Dacarbazine Ribonucleotide reductase Cell culture 030220 oncology & carcinogenesis Immunology Cancer research medicine.drug |
| Zdroj: | Journal of Investigative Dermatology. (2):453-460 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2010.310 |
| Popis: | Systemically delivered small interfering RNA (siRNA) therapies for cancer have begun clinical development. The effects of siRNA-mediated knockdown of ribonucleotide reductase subunit-2 (RRM2), a rate-limiting enzyme in cell replication, were investigated in malignant melanoma, a cancer with a paucity of effective treatment options. A panel of human melanoma cell lines was transfected with siRNA to induce the knockdown of RRM2. Sequence-specific, siRNA-mediated inhibition of RRM2 effectively blocked cell proliferation and induced G1/S-phase cell cycle arrest. This effect was independent of the activating oncogenic mutations in the tested cell lines. Synergistic inhibition of melanoma cell proliferation was achieved using the combination of siRNA targeting RRM2 and temozolomide, an analog of the current standard of care for melanoma chemotherapy. In conclusion, siRNA-mediated RRM2 knockdown significantly inhibits proliferation of melanoma cell lines with different oncogenic mutations with synergistic enhancement in combination with temozolomide. |
| Databáze: | OpenAIRE |
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