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

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  • Additional Information
    • Source:
      Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: Athens, Greece : D. A. Spandidos
    • Subject Terms:
      Gene Expression Regulation, Neoplastic*; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Butadienes/*pharmacology ; Fluorouracil/*pharmacology ; MAP Kinase Kinase 1/*genetics ; Nitriles/*pharmacology ; Oxaliplatin/*pharmacology; Aged ; Cell Line, Tumor ; Cell Survival/drug effects ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Drug Synergism ; Endonucleases/genetics ; Endonucleases/metabolism ; Female ; Histones/genetics ; Histones/metabolism ; Humans ; MAP Kinase Kinase 1/antagonists & inhibitors ; MAP Kinase Kinase 1/metabolism ; Male ; Middle Aged ; Mutation ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Signal Transduction ; Thymidylate Synthase/genetics ; Thymidylate Synthase/metabolism
    • Abstract:
      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 γH2AX 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.
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    • Contributed Indexing:
      Keywords: colorectal cancer; mitogen-activated protein kinase kinase inhibitor; oxaliplatin; 5-fluorouracil
    • Accession Number:
      0 (Butadienes)
      0 (DNA-Binding Proteins)
      0 (H2AX protein, human)
      0 (Histones)
      0 (Nitriles)
      0 (U 0126)
      04ZR38536J (Oxaliplatin)
      EC 2.1.1.45 (Thymidylate Synthase)
      EC 2.7.12.2 (MAP Kinase Kinase 1)
      EC 2.7.12.2 (MAP2K1 protein, human)
      EC 3.1.- (ERCC1 protein, human)
      EC 3.1.- (Endonucleases)
      U3P01618RT (Fluorouracil)
    • Publication Date:
      Date Created: 20181212 Date Completed: 20190524 Latest Revision: 20211018
    • Publication Date:
      20231215
    • Accession Number:
      PMC6323316
    • Accession Number:
      10.3892/mmr.2018.9730
    • Accession Number:
      30535504