PEG-conjugated hemoglobin with chemotherapy down regulate the EPO/EPOR expression in tumor xenograft model / 国际生物医学工程杂志

ABSTRACT

ObjectiveTo observe the influence of polyethylene glycol-conjugated hemoglobin (PEG-Hb) solution combined with cisplatin on the expression of erythropoietin/erythropoietin receptor (EPO/EPOR) and tumor angiogenesis in cancer treatment.MethodsHeLa cells were injected subcutaneously into the right oxter of 3-4 weeks old BALB/c nude mice to establish cervical tumor xenograft model.Then animals were randomly assigned to 4 groups (n=10) and treated respectivelygroup 1(control); group 2,cisplatin (5 mg/kg); group 3,PEG-Hb (0.6 g/kg); group 4 cisplatin (5 mg/kg) plus PEG-Hb (0.6 g/kg).The volume oftumors in each groups were measured in 4 weeks treatment period.Efficacy was measured as percent tumor growth inhibition (TGI) relative to salinetreated group.CD31 was detected by immunohistochemistry and its expression was identified as microvascular density (MVD).Expressions of hypoxia inducible factor-1α(HIF-1α) and EPO/EPOR in tumor tissues were analyzed by irnmunohistochemistry.EPOR protein level was tested by western blot.ELISA method was used in measuring EPO concentration in serum.ResultsTumor volume was significantly decreased in group 4 compared with other groups.Immunoreactivity data demonstrated lower expression of CD31,HIF-1α and EPO/EPOR in group 4.The expression of EPOR in the endothelial cells was also significantly decreased in group 4.Western-blot data indicated lower EPOR protein level in group 4.Serum level of EPO was also decreased in group 4.ConclusionPEG-Hb plus cisplatin is benefit to tumor tissue oxygenation,therefore it can inhibit the tumor angiogenesis and down regulate the erythropoietin/erythropoietin receptor system.The result can provide more evidence for the enhanced sensitivity effect of the artificial oxygen carrier in cancer therapy.