Multitarget therapy of malignant cancers by the head-to-tail tandem array multiple shRNAs expression system
| Autor: | Chuan Fu Hung, Tsung Lin Cheng, Wen-Hui Tsai, H. C. Hsu, Wen Tsan Chang, Chin-Wei Yeh, Chiao-Fang Teng, M. P. Wu |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Cancer Research RNA Untranslated Cell Survival Genetic Vectors Cell Transfection Small hairpin RNA HeLa RNA interference Cell Line Tumor Neoplasms medicine Humans RNA Small Interfering Molecular Biology Gene Cells Cultured Cell Proliferation Expression vector Models Genetic biology HEK 293 cells Prostatic Neoplasms biology.organism_classification Molecular biology medicine.anatomical_structure Cancer research Molecular Medicine RNA Interference Signal transduction HeLa Cells |
| Zdroj: | Cancer Gene Therapy. 16:516-531 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/cgt.2008.102 |
| Popis: | Coexpression of multiple shRNAs can simultaneously inhibit multiple genes or target multiple sites on a single gene. These approaches can be used for dissecting complex signaling pathways and even be applied to targeting multiple genes in cancer therapy. Here we established a simple and efficient multiple shRNAs expression system based on pSUPER, the most popular expression vector in mammalian cells. A series of head-to-tail tandem array multiple shRNAs expression vectors were constructed containing different combinations of six shRNA expression cassettes targeting genes involved in cell proliferation and survival pathways: Bcl-2, Survivin, Akt1, Erk2, CyclinE and NFkappaB. In HeLa and HEK293 cells, the multiple shRNAs expression constructs could efficiently and simultaneously induce inhibition of all six genes. We further evaluated the inhibition effects of the multiple shRNAs expression vectors on the human prostate cancer cell line PC3, which contains different cell variants with distinct oncogenic signaling alterations. The results revealed that the multiple shRNAs expression system could inhibit all six genes and was much more efficient in inducing apoptosis in the PC3 cells. Our results suggest that the multitarget shRNAs expression system could be an effective strategy in cancer therapy and be applied to any other DNA vector-based shRNA expression system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|