New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin
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 doxorub...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2020-12, Vol.475 (1-2), p.285-299 |
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| creator | Ciocan-Cȃrtiţă, Cristina Alexandra Jurj, Ancuţa Raduly, Lajos Cojocneanu, Roxana Moldovan, Alin Pileczki, Valentina Pop, Laura-Ancuta Budişan, Liviuţa Braicu, Cornelia Korban, Schuyler S. Berindan-Neagoe, Ioana |
| description | 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). |
| doi_str_mv | 10.1007/s11010-020-03881-w |
| format | Article |
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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).</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-020-03881-w</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Breast cancer ; Cancer therapies ; Cardiology ; Cell activation ; Cell death ; Cell growth ; Cell morphology ; Cell proliferation ; Chemotherapy ; Combined treatment ; Cytology ; Doxorubicin ; Gene expression ; Gene silencing ; Genes ; Interleukin 6 ; Life Sciences ; Medical Biochemistry ; Mitochondria ; Morphology ; Oncology ; siRNA ; Transcription activation ; Transforming growth factor-b1</subject><ispartof>Molecular and cellular biochemistry, 2020-12, Vol.475 (1-2), p.285-299</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c267w-c5cee8c84386e50bc3d4b5706eccc7e9312e661879b8aa9ee2cfab19e16776123</citedby><cites>FETCH-LOGICAL-c267w-c5cee8c84386e50bc3d4b5706eccc7e9312e661879b8aa9ee2cfab19e16776123</cites><orcidid>0000-0002-3055-4747</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11010-020-03881-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11010-020-03881-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Ciocan-Cȃrtiţă, Cristina Alexandra</creatorcontrib><creatorcontrib>Jurj, Ancuţa</creatorcontrib><creatorcontrib>Raduly, Lajos</creatorcontrib><creatorcontrib>Cojocneanu, Roxana</creatorcontrib><creatorcontrib>Moldovan, Alin</creatorcontrib><creatorcontrib>Pileczki, Valentina</creatorcontrib><creatorcontrib>Pop, Laura-Ancuta</creatorcontrib><creatorcontrib>Budişan, Liviuţa</creatorcontrib><creatorcontrib>Braicu, Cornelia</creatorcontrib><creatorcontrib>Korban, Schuyler S.</creatorcontrib><creatorcontrib>Berindan-Neagoe, Ioana</creatorcontrib><title>New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><description>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).</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cardiology</subject><subject>Cell activation</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Cell morphology</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Combined treatment</subject><subject>Cytology</subject><subject>Doxorubicin</subject><subject>Gene expression</subject><subject>Gene silencing</subject><subject>Genes</subject><subject>Interleukin 6</subject><subject>Life Sciences</subject><subject>Medical Biochemistry</subject><subject>Mitochondria</subject><subject>Morphology</subject><subject>Oncology</subject><subject>siRNA</subject><subject>Transcription activation</subject><subject>Transforming growth 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| subjects | Biochemistry Biomedical and Life Sciences Breast cancer Cancer therapies Cardiology Cell activation Cell death Cell growth Cell morphology Cell proliferation Chemotherapy Combined treatment Cytology Doxorubicin Gene expression Gene silencing Genes Interleukin 6 Life Sciences Medical Biochemistry Mitochondria Morphology Oncology siRNA Transcription activation Transforming growth factor-b1 |
| title | New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin |
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