Tumor Biology

, Volume 35, Issue 9, pp 9269–9279

MEK inhibitor effective against proliferation in breast cancer cell

Research Article

DOI: 10.1007/s13277-014-1901-5

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


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.


AZD6244Breast cancermiR-203CUL1

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, ShanghaiShanghai CityChina
  2. 2.Genetic Engineering Institute of Southern Medical UniversityGuangzhou CityChina
  3. 3.Hematology Department of Zhujiang Hospital affiliated to Southern Medical UniversityGuangzhou CityChina