Characterization of a novel HDAC/RXR/HtrA1 signaling axis as a novel target to overcome cisplatin resistance in human no
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RESEARCH
Open Access
Characterization of a novel HDAC/RXR/ HtrA1 signaling axis as a novel target to overcome cisplatin resistance in human non-small cell lung cancer Wenjing Wang1,2†, Mengyue Zhao1,2†, Lijuan Cui1,2†, Yong Ren3, Jingyuan Zhang1,2, Junli Chen1,2, Lina Jia1,2, Jiayu Zhang1,2, Jingyu Yang1,2, Guoliang Chen4, Charles R. Ashby Jr5, Chunfu Wu1,2*, Zhe-Sheng Chen5* and Lihui Wang1,2*
Abstract Background: Cisplatin is a first-line drug for the treatment of human non-small cell lung cancer (NSCLC); however, the majority of patients will develop drug resistance after treatment. In order to overcome cisplatin resistance, it is important to understand the mechanisms underlying the resistance. Methods: A gene microarray was used to screen for genes related to cisplatin resistance in NSCLC cell lines. Subsequently, the correlation between the HDAC, RXR and HtrA1 genes, in NSCLC, were verified using gene manipulation. Immunohistochemical staining was used to detect HDAC, RXR and HtrA1 expression in NSCLC specimens. Proliferation, migration and invasion assays were performed in vitro and in vivo to determine the role of the HDAC/RXR/HtrA1 signaling axis in cisplatin resistance, and luciferase reporter analysis and ChIP assays were performed to ascertain the mechanisms by which HDAC and RXR regulate the expression of HtrA1. Furthermore, in vitro and in vivo experiments were conducted in NSCLC cisplatin-resistant NSCLC to elucidate the effect of the low molecular weight compound, DW22, which targets the NSCLC cisplatin resistance HDAC/RXR/HtrA1 signaling pathway. (Continued on next page)
* Correspondence: [email protected]; [email protected]; [email protected] † Wenjing Wang, Mengyue Zhao and Lijuan Cui contributed equally to this work. 1 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China 5 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Newyork, NY 11439, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available
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