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

Cornelia Braicu,Sergiu Chira,Valentina Pileczki,Patriciu Achimas-Cadariu,Roxana Cojocneanu Petric,Eve Pointiere,Ioana Berindan-Neagoe,Laura Pop,Sumitra Deb

doi:10.1371/journal.pone.0120936

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.

Highlights

Of all cancers, breast cancer has the highest incidence and mortality rate in Europe according to data from 2012 [1]
15–20% of breast cancer cases are diagnosed as triplenegative breast cancer (TNBC), a highly aggressive clinical phenotype characterized by a lack of human epidermal growth factor receptor-2 (HER-2) overexpression, as well as a lack of PLOS ONE | DOI:10.1371/journal.pone
Using qRT-PCR array technology, we examined the transcript levels of 84 genes involved in apoptosis from the Hs578T-cell line transfected with p53 siRNA and incubated with EGCG

Summary

Introduction

Breast cancer has the highest incidence and mortality rate in Europe according to data from 2012 [1]. 15–20% of breast cancer cases are diagnosed as triplenegative breast cancer (TNBC), a highly aggressive clinical phenotype characterized by a lack of human epidermal growth factor receptor-2 (HER-2) overexpression, as well as a lack of PLOS ONE | DOI:10.1371/journal.pone.0120936. P53 siRNA and EGCG Dual Targeted Therapy. INNOVATION 2007–2013 (PNII) with title: “Modulation of pro/anticarcinogenic effect of toxic chemical agents in breast cancer multitargeted therapy (CANCERTER-p53). 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

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