MEK inhibitor enhanced the antitumor effect of oxaliplatin and 5-fluorouracil in MEK1 Q56P-mutant colorectal cancer cells

摘要

Mitogen-activated protein kinase kinase (MEK) small molecule inhibitors have been investigated in preclinical or clinical trials for the treatment of cancer. In the present study the genetic test results of 120 patients with colorectal cancer (CRC) were screened and the mutation rate of MEK1 was identified to be 1.67%. MEK inhibition by U0126 significantly decreased the growth of SW48 cells that harbored the MEK1 Q56P mutation, although it did not evidently affect the growth of NCI-H508 cells with MEK1 wild-type. In addition, U0126 increased the sensitivity of SW48 cells to 5-fluorouracil (5-FU) and oxaliplatin by producing more H2AX foci and decreasing the expression of excision repair cross-complementation group 1 and thymidylate synthase. The results suggested that MEK inhibitors in combination with oxaliplatin/5-FU may offer an improved therapeutic effect in patients with MEK-mutant CRC.