Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on ERK in BRAF mutant colon cancer cells.
Authors
SUN MIN LIM ; JEE WON HWANG ; JOONG BAE AHN ; SOO KYUNG BAE ; CHAN HEE PARK ; KI-YEOL KIM ; SUN YOUNG RHA ; HYUN CHEOL CHUNG ; JAE KYUNG ROH ; SANG JOON SHIN
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.