Journal
CANCER SCIENCE
Volume 100, Issue 9, Pages 1708-1713Publisher
WILEY
DOI: 10.1111/j.1349-7006.2009.01217.x
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [30870298, 30600329]
- Natural Science Foundation [2007BB5443, 2007BB5444]
- Chongqing Municipal Education Committee [KJ070510]
- Doctor Foundation of Chongqing University of Post and Telecommunications [A2008-65]
Ask authors/readers for more resources
Chemotherapy resistance in solid tumors is broad and encompasses diverse unrelated drugs. Three-dimensional multicellular spheroids (MCSs) are a good model for studying in vitro drug resistance. In the current study, we investigated the role of focal adhesion kinase (FAK) in 5-fluorouracil (5-FU) chemoresistance in colon carcinoma MCS culture cells. The expression of FAK was inhibited significantly by specific small hairpin RNA targeting FAK. The suppression of FAK expression did not affect the growth of spheroid cells. However, silencing of FAK combined with 5-FU treatment significantly decreased the 50% inhibitory concentration (IC50) of 5-FU and markedly increased the population of apoptosis cells, which was associated with the reduction of the levels of Akt and nuclear factor-kappa B (NF-kappa B). Moreover, knockdown of FAK could inhibit tumor growth and increase the sensitivity of the tumor to 5-FU in the nude mouse xenograft. These results indicate that while not affecting cellular proliferation in the absence of 5-FU, RNA interference targeting FAK potentiated 5-FU-induced cytotoxicity in vitro and in vivo, and partially reversed multicellular resistance, which may contribute to its chemosensitizing effect through efficiently suppressing Akt/NF-kappa B activity. (Cancer Sci 2009; 100: 1708-1713).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available