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Downregulation of IGF-IR expression by RNAi inhibits proliferation and enhances chemosensitization of human colon cancer cells.
- Source :
-
International Journal of Colorectal Disease . Jan2010, Vol. 25 Issue 1, p9-16. 8p. 1 Color Photograph, 3 Graphs. - Publication Year :
- 2010
-
Abstract
- Colon cancer is the second leading cause of cancer death worldwide. Elevated expression of insulin-like growth factor-I receptor (IGF-IR) is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against IGF-IR in our study. The aim of this study was to examine the anti-proliferation and chemosensitization effects elicited by a decrease in the transcription and protein levels of IGF-IR by RNAi in SW480 colon cancer cells. A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting IGF-IR to reduce its expression in SW480 cells. Western blot analysis was used to measure the protein level of IGF-IR. We assessed the effects of IGF-IR silencing on cancer cell growth by a cell growth curve. The effect of the 5-fluorouracil (5-FU)-induced cell death by knockdown of IGF-IR was also investigated by methyl thiazolyl tetrazolium assay. Transfection of siRNA targeting IGF-IR was shown to reduce IGF-IR messenger RNA levels by 95%. Western blotting detected a similar inhibition of IGF-IR protein levels in those cells. The cells transfected with PKD-short hairpin RNA-IGF-IR-V2 significantly decreased cell growth and rendered cells more sensitive to chemotherapy. The highest proliferation inhibitory and chemosensitization ratios were 53 ± 2% and 1.78, respectively. This study indicates that downregulation of IGF-IR results in significant inhibition of tumor growth in vitro. It also provides a promising strategy to chemotherapy efficacy in human tumors and forming a basis for future in vivo trials. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01791958
- Volume :
- 25
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- International Journal of Colorectal Disease
- Publication Type :
- Academic Journal
- Accession number :
- 45472174
- Full Text :
- https://doi.org/10.1007/s00384-009-0783-2