Dual targeted therapy with p53 siRNA and Epigallocatechingallate in a triple negative breast cancer cell model

PLoS One. 2015 Apr 7;10(4):e0120936. doi: 10.1371/journal.pone.0120936. eCollection 2015.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive phenotype that is resistant to standard therapy. Thus, the development of alternative therapeutic strategies for TNBC is essential. The purpose of our in vitro study was to evaluate the impact of p53 gene silencing in conjunction with the administration of a natural compound, epigallocatechingallate (EGCG). RT2Profiler PCR Array technology was used to evaluate the impact of dual treatment on the main genes involved in apoptosis in the Hs578T cell culture model of TNBC. Gene expression analysis revealed 28 genes were significantly altered (16 upregulated and 12 downregulated) in response to combined p53 siRNA and EGCG treatment. Further analysis revealed that p53 siRNA and EGCG dual therapy leads to the activation of pro-apoptotic genes and the inhibition of pro-survival genes, autophagy, and cell network formation. These results indicate that this dual therapy targets both the apoptotic and angiogenic pathways, which may improve treatment effectiveness for tumors resistant to conventional treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Blotting, Western
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*
  • Triple Negative Breast Neoplasms / therapy*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Anticarcinogenic Agents
  • RNA, Messenger
  • RNA, Small Interfering
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Catechin
  • epigallocatechin gallate

Grants and funding

This work was financed by the Sectoral Operational Program for Increasing the Economic Competitiveness (POSCCE) 709/2010 grant with the title: “Clinical and economical impact of proteom and transcriptom molecular profiling in neoadjuvant therapy of triple negative breast cancer (BREASTIMPACT)”. Cornelia Braicu has received a research grant financed by THE NATIONAL PLAN FOR RESEARCH, DEVELOPMENT AND INNOVATION 2007–2013 (PNII) with title: “Modulation of pro/anticarcinogenic effect of toxic chemical agents in breast cancer multitargeted therapy (CANCERTER-p53). Valentina Pileczki, Laura Pop, and Roxana Cojocneanu Petric has received a fellowships under the frame of European Social Fund, Human Resources Development Operational Programme 2007–2013, project no. POSDRU/159/1.5/S/138776 with title: “Model colaborativ institutional pentru translatarea cercetarii stiintifice biomedicale in practica clinica-TRANCENT”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.