Sydor S, Jafoui S, Wingerter L, Swoboda S, Mertens JC, Gerken G, Canbay A, Paul A, Fingas CD. Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells. World J Gastroenterol 2017; 23(22): 4007-4015 [PMID: 28652654 DOI: 10.3748/wjg.v23.i22.4007]
Corresponding Author of This Article
Christian D Fingas, MD, PhD, Associate Professor, Department for General, Visceral and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany. christian.fingas@uk-essen.de
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jun 14, 2017; 23(22): 4007-4015 Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.4007
Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells
Svenja Sydor, Sami Jafoui, Lena Wingerter, Sandra Swoboda, Joachim C Mertens, Guido Gerken, Ali Canbay, Andreas Paul, Christian D Fingas
Svenja Sydor, Sami Jafoui, Lena Wingerter, Guido Gerken, Ali Canbay, Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany
Sandra Swoboda, Andreas Paul, Christian D Fingas, Department for General, Visceral and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany
Joachim C Mertens, Division of Gastroenterology and Hepatology, University Hospital Zurich, 8091 Zurich, Switzerland
Author contributions: Sydor S contributed to acquisition, analysis and interpretation of data, statistical analysis, drafting of the manuscript; Jafoui S contributed to acquisition and analysis of data; Wingerter L contributed to acquisition and analysis of data; Swoboda S contributed to acquisition and analysis of data; Mertens JC contributed to critical revision of the manuscript for important intellectual content, technical support; Gerken G contributed to obtained funding, critical revision of the manuscript for important intellectual content; Canbay A contributed to obtained funding, critical revision of the manuscript for important intellectual content; Paul A contributed to obtained funding, critical revision of the manuscript for important intellectual content; Fingas CD contributed to study concept and design.
Supported byDFG/German Research Foundation, No. FI 1630/3-1 and No. IFORES D/107114400 (to CDF).
Institutional review board statement: For this study no human or animal derived material was used. All performed experiments and shown data were assessed by using established cell lines and were performed according to good laboratory practice guidelines. The study was reviewed and approved by the University of Duisburg-Essen Institutional Review Board.
Institutional animal care and use committee statement: For this study we did not perform animal experiments or use experimental material derived from animals. Provision of an institutional animal care and use committee statement is not applicable in this case.
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: There are no additional data available.
Correspondence to: Christian D Fingas, MD, PhD, Associate Professor, Department for General, Visceral and Transplantation Surgery, University Hospital Essen, University Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany. christian.fingas@uk-essen.de
Telephone: +49-201-723 83676 Fax: +49-201-7231131
Received: January 13, 2017 Peer-review started: January 14, 2017 First decision: February 23, 2017 Revised: April 5, 2017 Accepted: May 9, 2017 Article in press: May 9, 2017 Published online: June 14, 2017 Processing time: 152 Days and 11.7 Hours
Core Tip
Core tip: This manuscript addresses the timely and topical roles of cell cycle/apoptosis modulating enzymes for the tumor biology of human cholangiocarcinoma. These data suggest that polo-like kinases -Inhibition by BI6727 (volasertib) sensitizes some cholangiocarcinoma cell lines to cisplatin-induced apoptosis. Our findings include an enhanced cytotoxic effect of cisplatin by co-treatment with BI6727 (volasertib) and results in decreased protein expression levels of the anti-apoptotic molecule Bcl-2, which appears to be mediated via proteasomal degradation. Taken together, these data reveal another pro-apoptotic mechanism of polo-like kinase inhibition emphasizing the potential therapeutic benefit of polo-like kinase inhibitors for the treatment of cholangiocarcinoma.
