TY - JOUR T1 - Combination of CYP Inhibitor with MEK/ERK Inhibitor Enhances the Inhibitory Effect on ERK in BRAF Mutant Colon Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 2499 LP - 2508 VL - 33 IS - 6 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 Y1 - 2013/06/01 UR - http://ar.iiarjournals.org/content/33/6/2499.abstract N2 - 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. ER -