Expression of CYP2A6 in Tumor Cells Augments Cellular Sensitivity to Tegafur

To examine the role of cytochrome P450 2A6 (CYP2A6) in the cellular sensitivity to an anti‐tumor prodrug, tegafur (FT), a CYP2A6 cDNA construct was transfected into cells of a colon cancer cell line, DLD‐1. CYP2A6‐expressing cells (DLD‐1/CYP2A6 cells) more efficiently catalyzed the conversion of FT to 5‐fluorouracil (5‐FU) (2.6‐fold) and the 7‐hydroxylation of coumarin (7.9‐fold) than cells transfected with a null construct (DLD‐1/null cells). These results indicated that the expressed CYP2A6 was functionally active. The extent of growth inhibition of the DLD‐1/CYP2A6 cells by FT was greater than that of DLD‐1/null cells; the difference between the DLD‐1/CYP2A6 and DLD‐1/null cells was statistically significant at the concentrations of 250, 500 and 1000 μM. 5‐FU, an active metabolite of FT, inhibited the growth of both types of cells to the same extent. Thus, intracellular expression of CYP2A6 can sensitize cells to FT.