PT  - JOURNAL ARTICLE
AU  - SUN MIN LIM
AU  - JEE WON HWANG
AU  - JOONG BAE AHN
AU  - SOO KYUNG BAE
AU  - CHAN HEE PARK
AU  - KI-YEOL KIM
AU  - SUN YOUNG RHA
AU  - HYUN CHEOL CHUNG
AU  - JAE KYUNG ROH
AU  - SANG JOON SHIN
TI  - Combination of CYP Inhibitor with MEK/ERK Inhibitor Enhances the Inhibitory Effect on ERK in BRAF Mutant Colon Cancer Cells
DP  - 2013 Jun 01
TA  - Anticancer Research
PG  - 2499--2508
VI  - 33
IP  - 6
4099  - http://ar.iiarjournals.org/content/33/6/2499.short
4100  - http://ar.iiarjournals.org/content/33/6/2499.full
SO  - Anticancer Res2013 Jun 01; 33
AB  - Background/Aim: To investigate mechanisms of discrepancy in response to a MEK/ERK inhibitor, U0126, in KRAS- and BRAF-mutant colorectal cancer cells. Materials and Methods: Multiparametric flow cytometry was performed on two colon cancer cell lines, HCT116 and HT29. Cells were treated with U0126, and phospho-specific antibodies were used to monitor ERK signaling. Results: HCT116 and HT29 cells were treated with increasing amounts of U0126. The western blot analysis revealed that by increasing the amount of U0126 resulted in inhibition of phospho-ERK, in HCT116 and to a lesser degree in HT29 cells. Microarray profiling identified CYP1A1 and 1A2 overexpression in HT29 cells and that inhibition of CYP1A1 with α-naphthoflavone and furanfylline restored sensitivity to U0126 in HT29 cells. Conclusion: Combination of a CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF-mutant colon cancer cells.