title: Truncated Bid Overexpression Induced by Recombinant Adenovirus Cre/LoxP System Suppresses the Tumorigenic Potential of CD133+Ovarian Cancer Stem Cells.
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.
authors.affiliation: Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Qifang
authors.initials: Q
authors.lastname: Long
authors.affiliation: Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Weipei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Weixian
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Gynecology and Obstetrics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu Province, P.R. China.
authors.forename: Ru
authors.initials: R
authors.lastname: Yang
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D059765:Homologous Recombination; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017384:Sequence Deletion; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D051023:BH3 Interacting Domain Death Agonist Protein