Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+ Ovarian Cancer Stem Cells

Author:

Long Qifang1,Zhu Weipei1,Zhou Jundong2,Wu Jinchang2,Lu Weixian3,Zheng Cui3,Zhou Dongmei3,Yu Ling3,Yang Ru3

Affiliation:

1. Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China

2. Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China

3. Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China

Abstract

Ovarian cancer is one of the most lethal malignant gynecologic tumors with a high relapse rate worldwide. Cancer stem cells (CSCs) have been identified in ovarian cancer and other malignant tumors as a small population of cells that are capable of self-renewal and multidifferentiation. CD133+ ovarian CSCs have been reported to be more tumorigenic and more resistant to chemotherapeutic treatment. Thus, CD133 has emerged as one of the most promising therapeutic markers for ovarian cancer treatment. In the current study, we constructed a recombinant adenovirus Cre/loxP regulation system to selectively introduce truncated Bid (tBid) expression specifically targeting CD133+ in ovarian CSCs. The results demonstrated that the coinfection of Ad-CD133-Cre and Ad-CMV-LoxP-Neo-LoxP-tBid significantly increased tBid expression in CD133+ ovarian CSCs. Moreover, the tBid overexpression induced by a recombinant adenovirus Cre/loxP system dramatically inhibited cell proliferation and invasion, significantly elevated cell apoptosis, and activated the mitochondrial apoptosis pathway in CD133+ ovarian CSCs. Additionally, recombinant adenovirus Cre/loxP system-mediated tBid overexpression suppressed the tumorigenic potential of CD133+ ovarian CSCs in a xenograft mouse model. In conclusion, our study successfully constructed a recombinant adenovirus Cre/loxP system and induced tBid overexpression in CD133+ ovarian CSCs, providing a new therapeutic approach for ovarian cancer treatment.

Publisher

Cognizant, LLC

Subject

Cancer Research,Oncology,General Medicine

Reference35 articles.

1. Cancer statistics, 2016;CA Cancer J Clin.,2016

2. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer;Cancer Cell,2013

3. Outcome and clinical management of 275 patients with advanced ovarian cancer International Federation of Obstetrics and Gynecology II to IV inside the European Ovarian Cancer Translational Research Consortium-OVCAD;Int J Gynecol Cancer,2013

4. Rectosigmoid resection at the time of primary cytoreduction for advanced ovarian cancer. A multi-center analysis of surgical and oncological outcomes;Gynecol Oncol.,2012

5. Role of cancer stem cells in the progression and heterogeneity of melanoma;Orv Hetil.,2016

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3