Combination of CYP inhibitor with MEK/ERK inhibitor enhances the inhibitory effect on erk in braf mutant colon cancer cells

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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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 a-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.

Original languageEnglish
Pages (from-to)2499-2508
Number of pages10
JournalAnticancer research
Volume33
Issue number6
Publication statusPublished - 2013 Jun

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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