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World J Surg Oncol. 2016 Jan 14;14(1):10. doi: 10.1186/s12957-015-0761-9.

Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer.

Author information

1
Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. lvjinyan333@qq.com.
2
Library, Liaoning University of International Business and Economics, Dalian, Liaoning, 116001, Peoples' Republic of China. hutaiyuan0812@sina.com.
3
Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. wangruoyu0812@sina.com.
4
Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. zhujinming232@tom.com.
5
Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Jie Fang Street,Zhongshan District, Dalian, Liaoning, 116001, Peoples' Republic of China. wanggangwg21@hotmail.com.

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.

PMID:
26762567
PMCID:
PMC4712526
DOI:
10.1186/s12957-015-0761-9
[Indexed for MEDLINE]
Free PMC Article

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