Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

Wei,Hongmei; Qin,Shukui; Yin,Xiaojin; Chen,Yali; Hua,Haiqing; Wang,Lin; Yang,Ningrong; Chen,Yingxia; Liu,Xiufeng

doi:10.3892/ol.2015.3134

Endostar inhibits ascites formation and prolongs survival in mouse models of malignant ascites

Authors:
- Hongmei Wei
- Shukui Qin
- Xiaojin Yin
- Yali Chen
- Haiqing Hua
- Lin Wang
- Ningrong Yang
- Yingxia Chen
- Xiufeng Liu
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Affiliations: Department of Oncology, Qingdao Central Hospital, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266042, P.R. China, Department of Oncology, 81st Hospital of the People's Liberation Army, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210002, P.R. China, Simcere Pharmaceutical Research Institute, Nanjing, Jiangsu 210042, P.R. China
Published online on: April 21, 2015 https://doi.org/10.3892/ol.2015.3134
Pages: 2694-2700

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Abstract

Endostar, a modified recombinant human endostatin, inhibits the growth of a variety of tumors by suppressing neovascularization. Vascular endothelial growth factor (VEGF) has an important role in malignant ascites formation. In order to determine whether Endostar can suppress the formation of ascites and prolong survival times, mouse models of malignant ascites were established using S180 and H22 tumor cells. The experimental mice were randomly divided into four groups: The three treatment groups received different doses of Endostar (4, 8 and 16 mg/kg), and the control group received 0.9% w/v NaCl. The volume of ascites, and the tumor cell, red blood cell (RBC), VEGF protein and mRNA content of the ascites was measured alongside the peritoneal permeability and the mouse survival time. In vitro analysis of cultured Endostar‑treated S180 and H22 cells was also performed in order to examine cellular proliferation and the level of VEGF secreted protein and mRNA. The results revealed that Endostar suppressed the ascites volume, decreased the level of tumor cells, RBCs and VEGF in the ascites fluid, and lowered the permeability of the peritoneum. The tumor cells collected from the ascites in the Endostar‑treated mice demonstrated a decrease in the expression of VEGF mRNA. The survival rates of the 8 and 16 mg/kg Endostar‑treated mice were longer than those of the controls. The in vitro experiments revealed a significant inhibition of VEGF protein secretion and VEGF mRNA by Endostar, but no effect on cellular proliferation. In conclusion, Endostar lowers ascites production by downregulating VEGF expression, and may therefore be effective for the treatment of malignant ascites.

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