Recombinant human endostatin, Endostar, enhances the effects of chemo-radiotherapy in a mouse cervical cancer xenograft model

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-1 alpha 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.