title: Adenovirus carrying TIMP-3: a potential tool for cervical cancer treatment.
abstract: OBJECTIVE
  Previous studies have demonstrated the pivotal roles of matrix metalloproteinases (MMPs) in cervical cancer progression. Tissue inhibitor of metalloproteinases-3 (TIMP-3) can inhibit all of MMPs, and its overexpression can retard many kinds of tumor growth. Especially, a potent bystander effect would make it to be more advisable for treating cervical cancer whose primary growth pattern is to invade adjacent structures. These characters prompted the authors to explore its further applicability in human cervical cancer.
  
  
  METHODS
  We constructed a replication deficient adenoviral vector carrying TIMP-3 (Ad-TIMP-3). It was transferred into different cervical cancer cell lines in vitro and was injected into the tumor xenografts of nude mice in vivo.
  
  
  RESULTS
  Overexpression of TIMP-3 by adenovirus vector arrested cervical cancer cells in G2/M phase. It also promoted growth inhibition of cancer cells by bystander effects. Ad-TIMP-3 infection produced a more potent cell killing effect than Ad-p53 (P<0.05). A synergic effect was observed when Ad-TIMP-3 and cisplatin (cDDP) were used in combination (D<1). In vivo, Ad-TIMP-3 could inhibit cervical cancer xenografts growth. Compared with Ad-TIMP-3 and cDDP groups, tumor growth in Ad-TIMP-3 combined with cDDP group was inhibited more significantly (P<0.05).
  
  
  CONCLUSIONS
  These findings indicated that Ad-TIMP-3 bear a therapeutic potential for cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, No.1 Shuaifuyuan, Dong Dan District, Beijing 100007, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Jinghe
authors.initials: J
authors.lastname: Lang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Ming
authors.initials: M
authors.lastname: Fu
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000258:Adenovirus Infections, Human / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D005260:Female; D016195:G2 Phase / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology; D023041:Xenograft Model Antitumor Assays
chemical_list: C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D002945:Cisplatin