Enhanced anti-tumor and anti-angiogenic effects of metronomic cyclophosphamide combined with Endostar in a xenograft model of human lung cancer

Wang,Rui; Qin,Shukui; Chen,Yuqing; Li,Yumei; Chen,Changjie; Wang,Zishu; Zheng,Rongsheng; Wu,Qiong

doi:10.3892/or.2012.1828

Enhanced anti-tumor and anti-angiogenic effects of metronomic cyclophosphamide combined with Endostar in a xenograft model of human lung cancer

Authors:
- Rui Wang
- Shukui Qin
- Yuqing Chen
- Yumei Li
- Changjie Chen
- Zishu Wang
- Rongsheng Zheng
- Qiong Wu
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Affiliations: Department of Medical Oncology, The Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, Jiangsu 210002, P.R. China, Department of Respiratory Diseases, The Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Department of Bioscience, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China
Published online on: May 22, 2012 https://doi.org/10.3892/or.2012.1828
Pages: 439-445
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Standard chemotherapy for advanced NSCLC has reached a therapeutic plateau. More effective strategies must be explored. The purpose of this study was to evaluate the role of metronomic chemotherapy combined with an angiogenesis inhibitor in non-small cell lung cancer (NSCLC). A total of 114 BALB/c nude mice were inoculated subcutaneously with human NSCLC cells (A549), and when xenograft tumors were palpable, mice were randomly injected with saline as controls (Ctrl), or treated with metronomic cyclophosphamide (MET CPA), recombinant human endostatin, Endostar (Endo), MET CPA combined with Endostar (MET CPA + Endo) or maximum tolerance dose of CPA (MTD CPA), respectively. The growth of xenograft tumors and mouse survival were monitored. The frequency of peripheral blood circulating endothelial cells (CECs), microvessel density (MVD) and pericyte coverage was determined using flow cytometry and immunofluorescence staining. In comparison with the controls, treatment with either drug significantly inhibited the growth of xenograft tumors in mice. Treatment with MET CPA or Endostar, but not with MTD CPA, significantly reduced the frequency of peripheral blood total and viable CECs and the value of MVD. Endostar also considerably reduced pericyte coverage in xenograft tumors. Moreover, MET CPA combined with Endostar further reduced the frequency of peripheral blood CECs, the value of MVD, and pericyte coverage, with concomitant delay in tumor growth and extension of mouse survival. Our results indicate that MET CPA combined with Endostar results in enhanced anti-tumor and anti-angiogenic effects in a xenograft model of human lung cancer. Combined therapy with metronomic chemotherapy and an angiogenesis inhibitor may serve as a promising treatment strategy for patients with advanced NSCLC.

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