title: Recombinant adeno-associated virus expressing a p53-derived apoptotic peptide (37AA) inhibits HCC cells growth in vitro and in vivo.
abstract: Recent studies have confirmed that a p53-derived apoptotic peptide (37AA) could act as a tumor suppressor inducing apoptosis in multiple tumor cells through derepressing p73. However, the tumor suppressive effects of recombinant adeno-associated virus (rAAV) expressing 37AA on HCC cells are still unknown. In this study, we successfully constructed a recombinant rAAV expressing 37AA. In vitro and in vivo assays showed that transfection of NT4-37AA/rAAV in HCC cells strongly suppressed cell proliferation, induced apoptosis, and up-regulated the cellular expression of p73. NT4-37AA/rAAV transfection markedly slowed Huh-7 xenografted tumor growth in murine. Pretreatment of HCC cells with p73 siRNA abrogated these effects of NT4-37AA/rAAV. Furthermore, we found that expression of p73 was upregulated and the formation of P73/iASSP complex was prevented when 37AA was introduced into HCC cells. Taken together, these results indicate that introduction of 37AA into HCC cells with a rAAV vector may lead to the development of broadly applicable agents for the treatment of HCC, and the mechanism may, at least in part, be associated with the upregulation of p73 expression and reduced level of P73/iASSP complex.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Otorhinolaryngology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jigang
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D014162:Transfection / Q000379:methods; D000072160:Tumor Protein p73 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D010446:Peptide Fragments; D034741:RNA, Small Interfering; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53
keywords: 37AA; HCC; P53; P73; recombinant adeno-associated virus