Oncology Medical News about human colon cancer HT-29 cells;resistance to 5-flourouracil;involvement of Nrf2

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Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells
European Journal of Cancer, 06/15/09

Akhdar H et al. – Study demonstrates that 5-Fluorouracil (5-FU) activates the Nrf2/ARE pathway which in turn induces cytoprotective genes and modulates chemosensitivity of HT-29 colon cancer cells, suggesting Nrf2 as a potential therapeutic target in 5-FU treatment of colon cancer.

Methods

Aim was to investigate the effects of 5-FU on cytoprotective systems in human colon HT-29 cells
Whether 5-FU activates the Nrf2/antioxidant response element pathway (involved in cytoprotection) was also investigated

Results

5-FU induced the expression of mRNAs encoding glutathione transferases and antioxidant enzymes
Translocation of Nrf2 into the nucleus after 5-FU exposure was demonstrated by IHC and WB
Using an ARE-driven reporter gene assay, activation of the luciferase activity by 5-FU was also evidenced
Moreover, transfection of HT-29 cells with siRNA directed against Nrf2 inhibited induction of Nrf2 target genes and increased 5-FU cytotoxicity

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