机构：[1]Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001[2]Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004[3]Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, P.R. China
Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133(+)) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133(+) ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133(+) ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133(+) ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133(+) ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133(+) ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.
基金：
The present study was supported by grants from the Natural
Science Foundation of Jiangsu Province (BK2012599), the
Suzhou Municipal Science and Technology Development
Project (SYSD2012088), and the Suzhou Key Medical Center
(SZZX201506).
第一作者机构：[1]Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001[2]Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, 16 Beita West Road, Suzhou, Jiangsu 215001, P.R. China
推荐引用方式(GB/T 7714)：
Qifang Long,Ru Yang,Weixian Lu,et al.Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133(+) ovarian cancer stem cells[J].ONCOLOGY REPORTS.2017,37(1):155-162.doi:10.3892/or.2016.5263.
APA：
Qifang Long,Ru Yang,Weixian Lu,Weipei Zhu,Jundong Zhou...&Jinchang Wu.(2017).Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133(+) ovarian cancer stem cells.ONCOLOGY REPORTS,37,(1)
MLA：
Qifang Long,et al."Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133(+) ovarian cancer stem cells".ONCOLOGY REPORTS 37..1(2017):155-162
