title: Anti-tumor effect of adenovirus-mediated gene transfer of pigment epithelium-derived factor on mouse B16-F10 melanoma.
abstract: BACKGROUND
  Angiogenesis plays an important role in tumor growth, invasion, and eventually metastasis. Antiangiogenic strategies have been proven to be a promising approach for clinical therapy for a variety of tumors. As a potent inhibitor of tumor angiogenesis, pigment epithelium-derived factor (PEDF) has recently been studied and used as an anticancer agent in several tumor models.
  
  
  METHODS
  A recombined adenovirus carrying PEDF gene (Ad-PEDF) was prepared, and its expression by infected cells and in treated animals was confirmed with Western blotting and ELISA, respectively. Its activity for inhibiting human umbilical vein endothelial cell (HUVEC) proliferation was tested using the MTT assay. C57BL/6 mice bearing B16-F10 melanoma were treated with i.v. administration of 5 x 108 IU/mouse Ad-PEDF, or 5 x 108 IU/mouse Ad-Null, or normal saline (NS), every 3 days for a total of 4 times. Tumor volume and survival time were recorded. TUNEL, CD31 and H&E stainings of tumor tissue were conducted to examine apoptosis, microvessel density and histological morphology changes. Antiangiogenesis was determined by the alginate-encapsulated tumor cell assay.
  
  
  RESULTS
  The recombinant PEDF adenovirus is able to transfer the PEDF gene to infected cells and successfully produce secretory PEDF protein, which exhibits potent inhibitory effects on HUVEC proliferation. Through inhibiting angiogenesis, reducing MVD and increasing apoptosis, Ad-PEDF treatment reduced tumor volume and prolonged survival times of mouse bearing B16-F10 melanoma.
  
  
  CONCLUSIONS
  Our data indicate that Ad-PEDF may provide an effective approach to inhibit mouse B16-F10 melanoma growth.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medicine School, Sichuan University, Chengdu, Sichuan, PR China. pingliyang@126.com
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Shi
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: He
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Cui
authors.forename: Shun-Tao
authors.initials: ST
authors.lastname: Luo
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics / Q000628:therapy / Q000821:virology; D004730:Endothelium, Vascular / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000628:therapy* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055806:Microvessels; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000970:Antineoplastic Agents; D005136:Eye Proteins; D008156:Luciferases; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor