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Departments of Obstetrics and Gynecology and Nephrology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States
Ministry of Education Key Laboratory of Diagnostic Medicine, The School of Laboratory Diagnostic Medicine, Chongqing Medical University, Chongqing, China
Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266061, China
Department of Spine Surgery, Second Xiangya Hospital, Central South University, Changsha, 410011, China
Department of Orthopaedic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
Department of Neurosurgery, The Affiliated Zhongnan Hospital, Wuhan University, Wuhan, 430072, China
Department of Surgery Section of Plastic Surgery, The University of Chicago Medical Center, Chicago, IL 60637, United States
Department of Surgery, The University of Chicago Medical Center, Chicago, IL 60637, United States
Cited By :1
Export Date: 9 March 2021
Correspondence Address: He, T.-C.; Molecular Oncology Laboratory, 5841 South Maryland Avenue, United States; email: tche@uchicago.edu
Correspondence Address: Qi, H.; Department of Obstetrics and Gynecology, China; email: qihongbo728@163.com
Funding details: P30CA014599
Funding details: National Institutes of Health, NIH, CA226303, T32 GM00-7281
Funding details: National Center for Advancing Translational Sciences, NCATS, UL1 TR000430
Funding text 1: The authors wish to thank Dr. Ernest Lengyel of The University of Chicago for providing human ovarian cancer cell lines OVCAR8, HeyA8, and the paclitaxel (PTX)-resistant HeyA8-MDR. The reported work was supported in part by research grants from the National Institutes of Health (CA226303 to TCH). WW was supported by the Medical Scientist Training Program of the National Institutes of Health (T32 GM00-7281). This project was also supported in part by The University of Chicago Cancer Center Support Grant (P30CA014599) and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430. TCH was supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund. Funding sources were not involved in the study design; in the collection, analysis and/or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
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The inhibition of BRAF activity sensitizes chemoresistant human ovarian cancer cells to paclitaxel-induced cytotoxicity and tumor growth inhibition
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Ovarian cancer is one of the most common cancers in women and the second most common cause of gynecologic cancer death in women worldwide. While ovarian cancer is highly heterogeneous in histological subtypes and molecular genetic makeup, epithelial ovarian cancer is the most common subtype. The clinical outcomes of ovarian cancer largely depend on early detection and access to appropriate surgery and systemic therapy. While combination therapy with platinum-based drugs and paclitaxel (PTX) remains the first-line systemic therapy for ovarian cancer, many patients experience recurrence and die of progressive chemoresistance. Thus, there is an unmet clinical need to overcome recurrent disease due to resistance to chemotherapies of ovarian cancer. Here, we investigated whether BRAF inhibitors (BRAFi) could sensitize PTX-resistant ovarian cancer cells to PTX, and thus would overcome the resistance to chemotherapies. We found that BRAF and several members of the RAS/MAPK pathways were upregulated upon PTX treatment in ovarian cancer cells, and that BRAF expression was significantly elevated in the PTX-resistant ovarian cancer cells. While the BRAFi vemurafenib (VEM) alone did not cause any significant cytotoxicity in PTX-resistant ovarian cancer cells, VEM significantly enhanced PTX-induced growth inhibition and apoptosis in a dose-dependent manner. Furthermore, VEM and PTX were shown to synergistically inhibit tumor growth and cell proliferation of PTX-resistant human ovarian cancer cells in vivo. Collectively, these findings strongly suggest that BRAFi may be exploited as synergistic sensitizers of paclitaxel in treating chemoresistant ovarian cancer. © 2020 E-Century Publishing Corporation. All rights reserved.
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<div class="JournalArticle Publication short-list"> <div class="authors"> <span class="author-name" > Zhao, L. </span> <span class="author-type"> </span> ; <span class="author-name" > Huang, L. </span> <span class="author-type"> </span> ; <span class="author-name" > Zhang, J. </span> <span class="author-type"> </span> ; <span class="author-name" > Fan, J. </span> <span class="author-type"> </span> ; <span class="author-name" > He, F. </span> <span class="author-type"> </span> ; <span class="author-name" > Zhao, X. </span> <span class="author-type"> </span> ; <span class="author-name" > Wang, H. </span> <span class="author-type"> </span> ; <span class="author-name" > Liu, Q. </span> <span class="author-type"> </span> ; <span class="author-name" > Shi, D. </span> <span class="author-type"> </span> ; <span class="author-name" > Ni, N. </span> <span class="author-type"> </span> et al. </div ><div class="title"><a href="/gui2/?mode=browse¶ms=publication;31907362" mtid="31907362" target="_blank">The inhibition of BRAF activity sensitizes chemoresistant human ovarian cancer cells to paclitaxel-induced cytotoxicity and tumor growth inhibition</a></div> <div class="pub-info"> <span class="journal-title">AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH</span> <span class="journal-volume">12</span> : <span class="journal-issue">12</span> <span class="page"> pp. 8084-8098. , 15 p. </span> <span class="year">(2021)</span> </div> <div class="pub-end"><div class="identifier-list"> <span class="identifiers"> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85099362377" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85099362377"> Scopus </a> </span> </span> </div> <div class="short-pub-prop-list"> <span class="short-pub-mtid"> Publication:31907362 </span> <span class="status-holder"><span class="status-data status-APPROVED"> Published </span></span> <span class="pub-core"> Citing </span> <span class="pub-type">Journal Article (Article ) </span> <!-- && !record.category.scientific --> <span class="pub-category">Scientific</span> </div> </div> </div><div class="JournalArticle Publication long-list">
<div class="authors">
<img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png">
<div class="autype autype0"> <span class="author-name" >Zhao L.
</span>
;
<span class="author-name" >Huang L.
</span>
;
<span class="author-name" >Zhang J.
</span>
;
<span class="author-name" >Fan J.
</span>
;
<span class="author-name" >He F.
</span>
;
<span class="author-name" >Zhao X.
</span>
;
<span class="author-name" >Wang H.
</span>
;
<span class="author-name" >Liu Q.
</span>
;
<span class="author-name" >Shi D.
</span>
;
<span class="author-name" >Ni N.
</span>
;
<span class="author-name" >Wagstaff W.
</span>
;
<span class="author-name" >Pakvasa M.
</span>
;
<span class="author-name" >Fu K.
</span>
;
<span class="author-name" >B Tucker A.
</span>
;
<span class="author-name" >Chen C.
</span>
;
<span class="author-name" >Reid R.R.
</span>
;
<span class="author-name" >Haydon R.C.
</span>
;
<span class="author-name" >Luu H.H.
</span>
;
<span class="author-name" >Shen L.
</span>
;
<span class="author-name" >Qi H. ✉
</span>
;
<span class="author-name" >He T.-C. ✉
</span>
</div>
</div>
<div class="title"><a href="/gui2/?mode=browse¶ms=publication;31907362" target="_blank">The inhibition of BRAF activity sensitizes chemoresistant human ovarian cancer cells to paclitaxel-induced cytotoxicity and tumor growth inhibition</a></div> <div> <span class="journal-title">AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH</span>
<span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1943-8141">1943-8141</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1943-8141">1943-8141</a>)</span>:
<span class="journal-volume">12</span> <span class="journal-issue">12</span>
<span class="page">
pp 8084-8098
</span> <span class="year">(2021)</span>
</div>
<div class="pub-footer">
<span class="language" xmlns="http://www.w3.org/1999/html">Language:
English
| </span>
<span class="identifiers">
<span class="id identifier oa_none" title="none">
<a style="color:blue" title="85099362377" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85099362377">
Scopus
</a>
</span>
</span>
<div class="publication-citation">
<a target="_blank" href="/api/publication?cond=citations.related;eq;31907362&sort=publishedYear,desc&sort=title">
Number of cited publications: 1
</a>
</div>
<div class="mtid"><span class="long-pub-mtid">Publication: 31907362</span>
| <span class="status-data status-APPROVED"> Published
</span>
Citing
| <span class="type-subtype">Journal Article
( Article
)
</span>
| <span class="pub-category">Scientific</span>
| <span class="publication-sourceOfData">Scopus</span>
</div>
<div class="lastModified">Last Modified: 2021.03.09. 15:28 Kinga Sonnevend (SE_AOK_Adm5_Élet_kutcsop, admin)
</div>
<pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: Departments of Obstetrics and Gynecology and Nephrology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, United States
Ministry of Education Key Laboratory of Diagnostic ...</pre>
</div></div>