title: In vivo growth suppression of CT-26 mouse colorectal cancer cells by adenovirus-expressed small hairpin RNA specifically targeting thymosin beta-4 mRNA.
abstract: Thymosin beta-4 (Tβ4) is known to be involved in tumorigenesis. Overexpression of this polypeptide has been observed in a wide variety of cancers, including colorectal carcinoma (CRC). Accordingly, Tβ4 has been proposed to be a novel therapeutic target for CRC, especially in its metastatic form. Although in vitro tumor-suppressive effects of Tβ4 gene silencing mediated by small hairpin RNA (shRNA) have already been demonstrated, the in vivo efficacy of such an approach has not yet been reported. Herein, we demonstrated that infection with recombinant adenovirus expressing an shRNA targeting Tβ4 markedly reduced the growth of and robustly induced apoptosis in CT-26 mouse CRC cells in culture. Additionally, tumors grown in nude mice from the CT-26 cells whose Tβ4 expression already been downregulated by virus infection were also drastically reduced. Most importantly, significant growth arrest of tumors derived from the parental CT-26 cells was observed after multiple intratumoral injections of these viruses. Together, our results show for the first time that in vivo silencing of Tβ4 expression by its shRNA generated after adenoviral infection can suppress CRC growth. These results further demonstrate the feasibility of treating CRC by a Tβ4 knockdown gene therapeutic approach.
authors.affiliation: 1] Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC [2] Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC [3] School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: T-C
authors.initials: TC
authors.lastname: Chao
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: L-C
authors.initials: LC
authors.lastname: Chan
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: S-Y
authors.initials: SY
authors.lastname: Ju
authors.affiliation: National Center of Excellence for General Clinical Trial and Research, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: M-C
authors.initials: MC
authors.lastname: Tang
authors.affiliation: 1] Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC [2] School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: P-M
authors.initials: PM
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: C-H
authors.initials: CH
authors.lastname: Tzeng
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Y
authors.initials: Y
authors.lastname: Su
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051379:Mice; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D013947:Thymosin / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013947:Thymosin; D000099201:Thymosin beta(4)