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Recombinant human endostatin, Endostar, enhances the effects of chemo-radiotherapy in a mouse cervical cancer xenograft model
Y. Jia1, M. Liu1, L. Cao2, X. Zhao1, J. Wu3, F. Lu4, Y. Li2, Y. He5, S. Ren3, Y. Ju3, Y. Wang4, Z. Li6,*
1 Oncology Department, Hebei General Hospital, Shijiazhuang, Hebei
2 Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei
3 Centre of Animal Experiments, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei
4 Department of Radiotherapy, Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei
5 Cancer Institute of Hebei Province, Shijiazhuang, Hebei
6 Second Department of Surgery, Fourth Hospital, Hebei Medical University, Shijiazhuang, Hebei (China)
Eur. J. Gynaecol. Oncol. 2011, 32(3), 316–324;
Published: 10 June 2011
Background: The effects of recombinant human endostatin, Endostar, combined with concurrent chemo-radiotherapy (CCRT) on tumor growth, angiogenesis and lymphangiogenesis in a mouse xenograft model of cervical cancer was investigated. Methods: HeLa cells were injected subcutaneously to establish mouse xenograft models and mice were treated with normal saline (control), CCRT with cisplatin (CDDP), Endostar, or a combination of Endostar and CCRT. Growth, metastasis, and angiogenesis of tumors was monitored. Results: Tumorogenic activity of tumor cells in the CCRT, Endostar and combination Endostar-CCRT treatment groups was markedly decreased compared with the activity in the NS group (p < 0.05). The most significant inhibition of tumor growth was observed in the Endostar with CCRT group. Lymph node metastases in the Endostar with CCRT group (12.5%) and Endostar alone group (25%) were lower compared to the CCRT group (42.8%) and NS group (66.7%; p < 0.05). Endostar was also found to inhibit tumor angiogenesis. Endostar induced apoptosis of HeLa cells in vivo, and inhibited expression of VEGF and HIF-1α in vivo and in vitro. Conclusion: Endostar enhanced the anti-cancer effect of CCRT in a mouse xenograft model of cervical cancer. These findings thus provide a new strategy to treat cervical cancer.
Recombinant human endostatin