title: Suppression of lung cancer in murine model: treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin.
abstract: BACKGROUND
  The sustained growth of tumors necessitates neovascularization. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in antiangiogenesis therapy for tumor. Cisplatin is normally administered in chemotherapy for lung cancer but accompanied with serious side effects. In the current study, we investigated a novel chemo-antiangiogenesis therapeutic strategy to both improve toxic effects on lung cancer cells and reduce damages to normal cells in the anti-tumor therapy.
  
  
  METHODS
  In vitro, we transduced LLC cells with Ad-hEndo and collected supernatants. Western blotting analysis of the supernatants revealed expression of endostatin. In vivo, to fully investigate the suppression effect on murine lung cancer of the combination therapy, we injected recombinant human endostatin adenovirus intratumorally plus a low dose of cisplatin intraperitoneally routinely. The tumor volume and survival time were observed. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. Assessment of apoptotic cells by the TUNEL assay was conducted in the tumor tissues.
  
  
  RESULTS
  The combination treatment significantly suppressed the tumor growth and prolonged survival time of the murine LLC tumor model. This anti-tumor activity was associated with decreased microvessel density and increased apoptotic index of tumor cells.
  
  
  CONCLUSIONS
  According to the results in this study, recombinant human endostatin adenovirus in combination with a low dose of cisplatin demonstrated apparent synergistic anti-tumor activity without marked toxicity. Thus, these observations may provide a rational alternative for lung cancer treatment.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Keyuan Fourth Road, Chengdu, Sichuan, PR China. cherry.bai2008@gmail.com
authors.forename: Rui Z
authors.initials: RZ
authors.lastname: Bai
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Ke
authors.initials: K
authors.lastname: Xie
authors.forename: Yu Q
authors.initials: YQ
authors.lastname: Wei
authors.forename: Yong S
authors.initials: YS
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Jing M
authors.initials: JM
authors.lastname: Su
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Liu
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Niu
authors.forename: Zhi W
authors.initials: ZW
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D000970:Antineoplastic Agents; D043169:Endostatins; D011994:Recombinant Proteins; D002945:Cisplatin