Recombinant adeno-associated virus expressing a p53-derived apoptotic peptide (37AA) inhibits HCC cells growth in vitro and in vivo

// Hongyong Zhang 1, * , Yufeng Wang 1, * , Yanxia Bai 2 , Yuan Shao 2 , Jigang Bai 1 , Zhenhua Ma 1 , Qingguang Liu 1 , Shengli Wu 1 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China 2 Department of Otorhinolaryngology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China * These authors contributed equally to this work Correspondence to: Qinguang Liu, email: liuqingguang@vip.sina.com Shengli Wu, email: victorywu2000@163.com Keywords: recombinant adeno-associated virus, P53, P73, HCC, 37AA Received: June 21, 2016      Accepted: January 24, 2017      Published: February 06, 2017 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.