title: Therapeutic effects of survivin dominant negative mutant in a mouse model of prostate cancer.
abstract: OBJECTIVE
  Patients with localized prostate cancer can usually achieve initial response to conventional treatment. However, most of them will inevitably progress to advanced disease stage. There is a clear need to develop innovative and effective therapeutics for prostate cancer. Mouse survivin T34A (mS-T34A) is a phosphorylation-defective Thr34 → Ala dominant negative mutant, which represents a potential promising target for cancer gene therapy. This study was designed to determine whether mS-T34A plasmid encapsuled by DOTAP-chol liposome (Lip-mS) has the anti-tumor activity against prostate cancer, if so, to further investigate the possible mechanisms.
  
  
  METHODS
  In vitro, TRAMP-C1 cells were transfected with Lip-mS and examined for apoptosis by PI staining and flow cytometric analysis. In vivo, subcutaneous prostate cancer models were established in C57BL/6 mice, which were randomly assigned into three groups to receive i.v. administrations of Lip-mS, pVITRO2-null plasmid complexed with DOTAP-chol liposome (Lip-null) or normal saline every 2 days for eight doses. Tumor volume was measured. Tumor tissues were inspected for apoptosis by TUNEL assay. Microvessel density (MVD) was determined by CD31 immunohistochemistry. Alginate-encapsulated tumor cell test was conducted to evaluate the treatment effect on angiogenesis.
  
  
  RESULTS
  Administration of Lip-mS resulted in significant inhibition in the growth of mouse TRAMP-C1 tumors. The anti-tumor response was associated with increased tumor cell apoptosis and decreased microvessel density.
  
  
  CONCLUSIONS
  The present study may be of importance in the exploration of the potential application of Lip-mS in the treatment of a broad spectrum of tumors.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Chengdu, Sichuan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Fei
authors.initials: F
authors.lastname: Leng
authors.forename: Qing-Zhong
authors.initials: QZ
authors.lastname: Yuan
authors.forename: Yan
authors.initials: Y
authors.lastname: Shan
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xiao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wen
authors.forename: Tian-Tai
authors.initials: TT
authors.lastname: Ma
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Mao
authors.forename: Han-Shuo
authors.initials: HS
authors.lastname: Yang
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D015316:Genetic Therapy; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000627:therapeutic use; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage; D012097:Repressor Proteins / Q000235:genetics* / Q000627:therapeutic use; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D005229:Fatty Acids, Monounsaturated; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; D012097:Repressor Proteins; D000077022:Survivin; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane