title: Systemic delivery of lentivirus-mediated secretable TAT-apoptin eradicates             hepatocellular carcinoma xenografts in nude mice.
abstract: Apoptin, a chicken anemia virus-derived protein, has been shown to induce apoptosis in various human cancer cell lines, but not in normal cells, thus making it a candidate for the development of novel therapeutic strategies. To enable the efficient transduction of tumor cells with apoptin, we have developed a novel mammalian expression system for the secretion of apoptin in vitro. We have previously shown the efficient and tumor-specific killing of cells by adding a secretory signal peptide (SP) to the N terminus of transacting activator of transcription (TAT)-apoptin (SP-TAT-apoptin). In addition, our report showed the successful secretion of high levels of TAT-apoptin/GFP into the culture medium from HUVEC cells infected by lentivirus LV-SP-TAT-apoptin/GFP. To obtain sustained apoptin-induced tumor cell death in vivo, we injected the LV-SP-TAT-apoptin viruses via the tail vein for systemic delivery of the viruses; viruses expressing LV-SP-TAT-GFP were used as a negative control. Markedly, almost all the hepatocellular carcinoma xenograft tumors disappeared following the treatment while the xenografts that received the control LV-SP-TAT-GFP viruses continued to grow. Moreover, the animal studies presented in this paper demonstrate a low toxicity of SP-TAT-apoptin in vivo, confirming and extending the results of the in vitro studies. Taken together, our data strongly suggest that systemic delivery of lentivirus-mediated secretable TAT-apoptin is feasible to eradicate liver cancer in vivo.
authors: Department of Oncology, the First Affiliated Hospital of Xi'an                     Jiaotong University Medical College, Xi'an, P.R. China.
authors: Jin-Lu
authors: JL
authors: Ma
authors: Su-Xia
authors: SX
authors: Han
authors: Jing
authors: J
authors: Zhao
authors: Dan
authors: D
authors: Zhang
authors: Li
authors: L
authors: Wang
authors: Yao-Dong
authors: YD
authors: Li
authors: Qing
authors: Q
authors: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002460:Cell Line; D015316:Genetic Therapy / Q000379:methods; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C091717:VP3 protein, Chicken anemia virus; D054322:tat Gene Products, Human Immunodeficiency Virus