PEG-conjugated Hemoglobin Combination with Cisplatin Enforced the Antiangiogeic Effect in a Cervical Tumor Xenograft Model

Abstract

Angiogenesis, an essential event involved in a tumor's progression and metastasis, is regulated by hypoxia. Hypoxia widely exists in solid tumors due to the abnormal vasculature of tumor tissue and insufficiency of tissue oxygenation. We speculate that hemoglobin-based oxygen carriers (HBOCs) can attenuate tissue hypoxia, thereby suppressingthe angiogenesis in solid tumor in the context that HBOCs have the ability to increase tissue oxygenation. In the present study, PEG-conjugated hemoglobin solution (0.3 g/kg i.v. or 0.6 g/kg i.v.) was intravenously administrated to BALB/c nude mice bearing the cervical tumor twice a week with or without the treatment of cisplatin (5mg/kg i.p.) to investigate whether PEG-conjugated hemoglobin has a chemo-sensitization effect though anti-angiogenesis pathway. Tumor volume was measured every three days and tumor hypoxia was detected by immunohistochemistry for Hypoxyprobe™-1. Anti-angiogenic effect was accessed by detection of mRNA and protein levels of vascular endothelial growth factor (VEGF), the most important angiogenic factor. Our results showed that high concentration of PEG-conjugated hemoglobin solution significantly impeded the growth of tumor when compared with the control group. Moreover, VEGF expression was declined when treated with PEG-conjugated hemoglobin, possibly through the HIF regulation system. Collectively, treatment of PEG-conjugated hemoglobin combination with cisplatin has an antiangiogeic effect, but the underlying mechanism should be further studied.

• Artificial oxygen carrier
• tumor
• hypoxia
• cisplatin
• angiogenesis