title: Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer.
abstract: BACKGROUND
  The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established.
  
  
  METHODS
  Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n=15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15+20, 15+10, and 15+5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment.
  
  
  RESULTS
  The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property.
  
  
  CONCLUSIONS
  The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. lvjinyan333@qq.com.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Lv
authors.affiliation: Library, Liaoning University of International Business and Economics, Dalian, Liaoning, 116001, Peoples' Republic of China. hutaiyuan0812@sina.com.
authors.forename: Tai-Yuan
authors.initials: TY
authors.lastname: Hu
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. wangruoyu0812@sina.com.
authors.forename: Ruo-Yu
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. zhujinming232@tom.com.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. wanggangwg21@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D043169:Endostatins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043169:Endostatins; D051880:Receptors, Notch; D003520:Cyclophosphamide