New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin

Cristina Alexandra Ciocan-Cȃrtiţă, Ancuţa Jurj, Lajos Raduly, Roxana Cojocneanu, Alin Moldovan, Valentina Pileczki, Laura Ancuta Pop, Liviuţa Budişan, Cornelia Braicu, Schuyler S. Korban, Ioana Berindan-Neagoe

Research output: Contribution to journalArticlepeer-review

Abstract

Triple-negative breast cancer (TNBC), which accounts for 10–20% of all breast cancers, has the worst prognosis. Although chemotherapy treatment is a standard for TNBC, it lacks a specific target. Therefore, new therapeutic strategies are required to be investigated. In this study, a combined doxorubicin (DOX) and small interfering RNA (siRNA) therapy is proposed as therapeutic strategy for targeting TGFβ1 gene. Hs578T cell line is used as in vitro model for TNBC, wherein TGFβ1siRNA therapy is employed to enhance therapeutic effects. Cell proliferation rate is measured using an MTT test, and morphological alterations are assed using microscopically approached, while gene expression is determined by qRT-PCR analysis. The combined treatment of TGFβ1siRNA and DOX reduced levels of cell proliferation and mitochondrial activity and promoted the alteration of cell morphology (dark-field microscopy). DOX treatment caused downregulation of six genes and upregulation of another six genes. The combined effects of DOX and TGFβ1siRNA resulted in upregulation of 13 genes and downregulation of four genes. Silencing of TGFβ1 resulted in activation of cell death mechanisms in Hs578T cells, to potentiate the effects of DOX, but not in an additive manner, due to the activation of genes involved in resistance to therapy (ABCB1 and IL-6).

Original languageEnglish (US)
Pages (from-to)285-299
Number of pages15
JournalMolecular and Cellular Biochemistry
Volume475
Issue number1-2
DOIs
StatePublished - Dec 1 2020

Keywords

  • Doxorubicin
  • TGFβ1
  • Triple-negative breast cancer
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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