Cargando…

RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA

Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug’s ability to silence expression suppresses the growth of cholang...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Kejun, Chen, Dong, Wang, Xingang, Zhang, Shaoyan, Wang, Jigang, Gao, Yuan, Yan, Bomin
Formato: Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039959/
https://www.ncbi.nlm.nih.gov/pubmed/21339993
http://dx.doi.org/10.3390/ijms12010385
_version_ 1782198254587346944
author Zhang, Kejun
Chen, Dong
Wang, Xingang
Zhang, Shaoyan
Wang, Jigang
Gao, Yuan
Yan, Bomin
author_facet Zhang, Kejun
Chen, Dong
Wang, Xingang
Zhang, Shaoyan
Wang, Jigang
Gao, Yuan
Yan, Bomin
author_sort Zhang, Kejun
collection PubMed
description Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug’s ability to silence expression suppresses the growth of cholangiocarcinoma cells and/or sensitizes cholangiocarcinoma cells to chemotherapeutic agents through induction of apoptosis. We targeted the Slug gene using siRNA (Slug siRNA) via full Slug cDNA plasmid (Slug cDNA) transfection of cholangiocarcinoma cells. Slug siRNA, cisplatin, or Slug siRNA in combination with cisplatin, were used to treat cholangiocarcinoma cells in vitro. Western blot was used to detect the expression of Slug, PUMA, and E-cadherin protein. TUNEL, Annexin V Staining, and cell cycle analysis were used to detect apoptosis. A nude mice subcutaneous xenograft model of QBC939 cells was used to assess the effect of Slug silencing and/or cisplatin on tumor growth. Immunohistochemical staining was used to analyze the expression of Slug and PUMA. TUNEL was used to detect apoptosis in vivo. The results showed that PUMA and E-cadherin expression in cholangiocarcinoma cells is Slug dependent. We demonstrated that Slug silencing and cisplatin both promote apoptosis by upregulation of PUMA, not by upregulation of E-cadherin. Slug silencing significantly sensitized cholangiocarcinoma cells to cisplatin through upregulation of PUMA. Finally, we showed that Slug silencing suppressed the growth of QBC939 xenograft tumors and sensitized the tumor cells to cisplatin through PUMA upregulation and induction of apoptosis. Our findings indicate that Slug is an important modulator of the therapeutic response of cholangiocarcinoma cells and is potentially useful as a sensitizer in cholangiocarcinoma therapy. One of the mechanisms is the regulation of PUMA by Slug.
format Text
id pubmed-3039959
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-30399592011-02-18 RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA Zhang, Kejun Chen, Dong Wang, Xingang Zhang, Shaoyan Wang, Jigang Gao, Yuan Yan, Bomin Int J Mol Sci Article Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug’s ability to silence expression suppresses the growth of cholangiocarcinoma cells and/or sensitizes cholangiocarcinoma cells to chemotherapeutic agents through induction of apoptosis. We targeted the Slug gene using siRNA (Slug siRNA) via full Slug cDNA plasmid (Slug cDNA) transfection of cholangiocarcinoma cells. Slug siRNA, cisplatin, or Slug siRNA in combination with cisplatin, were used to treat cholangiocarcinoma cells in vitro. Western blot was used to detect the expression of Slug, PUMA, and E-cadherin protein. TUNEL, Annexin V Staining, and cell cycle analysis were used to detect apoptosis. A nude mice subcutaneous xenograft model of QBC939 cells was used to assess the effect of Slug silencing and/or cisplatin on tumor growth. Immunohistochemical staining was used to analyze the expression of Slug and PUMA. TUNEL was used to detect apoptosis in vivo. The results showed that PUMA and E-cadherin expression in cholangiocarcinoma cells is Slug dependent. We demonstrated that Slug silencing and cisplatin both promote apoptosis by upregulation of PUMA, not by upregulation of E-cadherin. Slug silencing significantly sensitized cholangiocarcinoma cells to cisplatin through upregulation of PUMA. Finally, we showed that Slug silencing suppressed the growth of QBC939 xenograft tumors and sensitized the tumor cells to cisplatin through PUMA upregulation and induction of apoptosis. Our findings indicate that Slug is an important modulator of the therapeutic response of cholangiocarcinoma cells and is potentially useful as a sensitizer in cholangiocarcinoma therapy. One of the mechanisms is the regulation of PUMA by Slug. Molecular Diversity Preservation International (MDPI) 2011-01-14 /pmc/articles/PMC3039959/ /pubmed/21339993 http://dx.doi.org/10.3390/ijms12010385 Text en © 2011 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhang, Kejun
Chen, Dong
Wang, Xingang
Zhang, Shaoyan
Wang, Jigang
Gao, Yuan
Yan, Bomin
RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title_full RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title_fullStr RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title_full_unstemmed RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title_short RNA Interference Targeting Slug Increases Cholangiocarcinoma Cell Sensitivity to Cisplatin via Upregulating PUMA
title_sort rna interference targeting slug increases cholangiocarcinoma cell sensitivity to cisplatin via upregulating puma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039959/
https://www.ncbi.nlm.nih.gov/pubmed/21339993
http://dx.doi.org/10.3390/ijms12010385
work_keys_str_mv AT zhangkejun rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT chendong rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT wangxingang rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT zhangshaoyan rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT wangjigang rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT gaoyuan rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma
AT yanbomin rnainterferencetargetingslugincreasescholangiocarcinomacellsensitivitytocisplatinviaupregulatingpuma