Molecular and Cellular Biochemistry

, Volume 381, Issue 1, pp 61–68

p53siRNA therapy reduces cell proliferation, migration and induces apoptosis in triple negative breast cancer cells

  • Cornelia Braicu
  • Valentina Pileczki
  • Alexandru Irimie
  • Ioana Berindan-Neagoe
Article

DOI: 10.1007/s11010-013-1688-5

Cite this article as:
Braicu, C., Pileczki, V., Irimie, A. et al. Mol Cell Biochem (2013) 381: 61. doi:10.1007/s11010-013-1688-5

Abstract

p53 protein is probably the best known tumor suppressor. Earlier reports proved that human breast cancer cells expressing mutant p53 displayed resistance to apoptosis. This study is intended to investigate, the potential applications of RNA interference (RNAi) to block p53 expression, as well as its subsequent effect on cell growth, apoptosis and migration on a triple negative human breast cancer cell line (Hs578T). p53siRNA significantly reduced cell index (CI) compared to the control and we observed an inhibition of cellular migration in the interval of time between 0 and 30 h, as shown in the data obtained by dynamic evaluation using the xCELLigence System. Also, by using PCR-array technology, a panel of 84 key genes involved in apoptosis was investigated. Our studies indicate that the knockdown of p53 expression by siRNA modulates several genes involved in cell death pathways and apoptosis, showing statistically significant gene expression differences for 22 genes, from which 18 were upregulated and 4 were downregulated. The present research also emphasizes the important role of BCL-2 pro-apoptotic family of genes (Bim, Bak, and Bax) in activating apoptosis and reducing cell proliferation by p53siRNA treatment. Death receptors cooperate with BCL-2 pro-apoptotic genes in reducing cell proliferation. The limited success may be due to the activation of the antiapoptotic gene Mcl-1, and it may be associated with the resistance of triple negative breast cancer cells to cancer treatment. Thus, targeting p53siRNA pathways using siRNA may serve as a promising therapeutic strategy for the treatment of breast cancers.

Keywords

p53siRNATriple negative breast cellsCell proliferationMigrationApoptosis

Supplementary material

11010_2013_1688_MOESM1_ESM.pptx (252 kb)
Supplementary material 1 (PPTX 252 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Cornelia Braicu
    • 1
    • 2
  • Valentina Pileczki
    • 1
  • Alexandru Irimie
    • 3
    • 4
  • Ioana Berindan-Neagoe
    • 1
    • 2
    • 5
  1. 1.Research Center for Functional Genomics, Biomedicine and Translational Medicine“Iuliu Hatieganu” University of Medicine and PharmacyCluj-NapocaRomania
  2. 2.Department of Functional Genomics and Experimental PathologyThe Oncological Institute “Prof. Dr. Ion Chiricuta”Cluj-NapocaRomania
  3. 3.Department of Surgical Oncology“I. Hatieganu” University of Medicine and PharmacyCluj-NapocaRomania
  4. 4.Department of SurgeryThe Oncological Institute“Prof. Dr.Ion Chiricuta”Cluj-NapocaRomania
  5. 5.Department of Immunology“Iuliu Hatieganu” University of Medicine and PharmacyCluj-NapocaRomania