Secretory expression of p53(N15)-Ant following lentivirus-mediated gene transfer induces cell death in human cancer cells |
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Authors: | Li Yueping Qiu Shudong Song Liping Yan Qingfeng Yang Guangxiao |
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Affiliation: | a Department of Anatomy and Histology and Embryology, Center for Reproductive Medicine, Medical College of Xi'an Jiaotong University, Xi'an, Shanxi, P. R. Chinab Department of Radiation Therapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi, P. R. Chinac Department of Cardiac Surgery, The Affiliated Hospital of Hainan Medical College, Haikou, P. R. Chinad Xi'an Huaguang Bio-engineering Co., Xi'an, Shanxi, P. R. China |
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Abstract: | p53 (N15)-Ant 32-peptide has been considered a novel and effective peptide for cancer therapy. To further enhance its anticancer effect and overcome the limitation of peptide therapy, a recombinant lentivirus was constructed in this study with the following strategies: the secretory expression of therapeutic peptide and lentivirus gene transfer system. The results demonstrated that LV-NT4(Si)-p53 (N15)-Ant could significantly suppress cell growth and induce rapid cell death in MCF-7 (overexpressed wild-type p53), HepG2(wide-type p53), OVCAR-3 (mutant type p53) and H1299 (null p53)cells in time-dependent manners through successful gene transfer and secretory expression of therapeutic peptide at 48 h post-infection. Transmission electron microscopy and flow cytometric analysis revealed that LV-NT4(Si)-p53 (N15)-Ant could induce two different kinds of cell death (necrosis and apoptosis) by two different mechanisms, since p53 (N15)-Ant peptide has the potential of blocking interaction of mdm-2 with other protein target, and on the other hand, it could form S-shape helix-loop-helix structures, which is able to rapidly disrupt cancer cell membranes. Based on these finding, LV-NT4 (Si)-p53 (N15)-Ant may be a novel recombinant virus because it induces cell death by two different pathways. |
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Keywords: | Recombinant lentivirus Secretory expression p53 Cancer gene therapy |
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