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

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 respectively:group 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.

Influence of chemical hypoxia induced by cobalt chloride on the proliferation and apoptosis of tumor cells / 基础医学与临床

Objective To investigate the effect of cobalt chloride on tumor cell proliferation and apoptosis in vitro, to explore the reasonable strategy of chemical hypoxia induced by CoCl2. Methods Two tumor cell lines (A549 and HeLa) were respectively exposed to CoCl2(0.05～2 mmol/L) for different time period (4～48 h), cells viability、proliferation and apoptosis were maesured by MTT and FCM methods. HIF-1? and related apoptosis proteins expression were detected by Western blot. Results Cells viability was weakly changed in low concentration(≤200 ?mol/L)of CoCl2 within 24 h. However, higher dose or prolonged challenge of CoCl2 significantly decreased cell survival rate (P