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Tumor Biology

, Volume 35, Issue 9, pp 9269–9279 | Cite as

MEK inhibitor effective against proliferation in breast cancer cell

  • Yan Zhou
  • Hai-yan Hu
  • Wei Meng
  • Ling Jiang
  • Xing Zhang
  • Jing-jing Sha
  • Zhigang Lu
  • Yang Yao
Research Article

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

AZD6244 Breast cancer miR-203 CUL1 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81072176 and 81372873).

Conflicts of interest

None.

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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

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