Tumor Biology

, Volume 35, Issue 9, pp 9269–9279

MEK inhibitor effective against proliferation in breast cancer cell

Authors

  • Yan Zhou
    • Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • Hai-yan Hu
    • Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
  • Wei Meng
    • Genetic Engineering Institute of Southern Medical University
  • Ling Jiang
    • Genetic Engineering Institute of Southern Medical University
  • Xing Zhang
    • Hematology Department of Zhujiang Hospital affiliated to Southern Medical University
  • Jing-jing Sha
    • Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
    • Hematology Department of Zhujiang Hospital affiliated to Southern Medical University
    • Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai
Research Article

DOI: 10.1007/s13277-014-1901-5

Cite this article as:
Zhou, Y., Hu, H., Meng, W. et al. Tumor Biol. (2014) 35: 9269. doi:10.1007/s13277-014-1901-5

Abstract

The targeted small-molecule drug AZD6244 is an allosteric, ATP-noncompetitive inhibitor of MEK1/2 that has shown activity against several malignant tumors. Here, we report that AZD6244 repressed cell growth and induced apoptosis and G1-phase arrest in the breast cancer cell lines MDA-MB-231 and HCC1937. Using microRNA (miRNA) arrays and quantitative RT-PCR, we found that miR-203 was up-regulated after AZD6244 treatment. In accordance with bioinformatics and luciferase activity analyses, CUL1 was found to be the direct target of miR-203. Furthermore, miR-203 inhibition and CUL1 overexpression reversed the cytotoxicity of AZD6244 on the MDA-MB-231 and HCC1937 cells. Collectively, our data indicate that miR-203 mediates the AZD6244-induced cytotoxicity of breast cancer cells and that the MEK/ERK/miR-203/CUL1 signaling pathway may participate in this process.

Keywords

AZD6244Breast cancermiR-203CUL1

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014