TY - JOUR
T1 - New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin
AU - Ciocan-Cȃrtiţă, Cristina Alexandra
AU - Jurj, Ancuţa
AU - Raduly, Lajos
AU - Cojocneanu, Roxana
AU - Moldovan, Alin
AU - Pileczki, Valentina
AU - Pop, Laura Ancuta
AU - Budişan, Liviuţa
AU - Braicu, Cornelia
AU - Korban, Schuyler S.
AU - Berindan-Neagoe, Ioana
N1 - Funding Information:
This paper was published under the frame of European Social Found, Human Capital Operational Programme 2014–2020, Project No. POCU/380/6/13/125171, and PNCDI III 2015–2020 “Increasing the performance of scientific research and technology transfer in translational medicine through the formation of a new generation of young researchers”—ECHITAS, no. 29PFE/ 18.10. 2018. Cristina Alexandra Ciocan-Cȃrtiţă received a grant for doctoral research Grant Number 1300/11/13.01.2017.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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).
AB - 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).
KW - Doxorubicin
KW - TGFβ1
KW - Triple-negative breast cancer
KW - siRNA
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U2 - 10.1007/s11010-020-03881-w
DO - 10.1007/s11010-020-03881-w
M3 - Article
C2 - 32888160
AN - SCOPUS:85090160815
VL - 475
SP - 285
EP - 299
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -