Influence of PEG-conjugated hemoglobin on tumor oxygenation and response to chemotherapy.

Hypoxic tumors are significantly more malignant, metastatic, radio- and chemoresistant. The use of artificial oxygen carriers represents a new approach to the problem of hypoxia. In the present study, female athymic BALB/c nude mice bearing the cervical carcinoma were untreated or treated with cisplatin to determine whether administration of artificial oxygen carrier (PEG-conjugated Hemoglobin, PEG-Hb) could improve the tumor oxygenation and enhance the anti-tumor efficacy of cisplatin. Pimonidazole staining was employed to detect tumor tissue oxygenation status. We found that the application of a higher dose (0.6 g/kg) PEG-Hb could significantly ameliorate the hypoxic condition in cervical carcinoma xenograft models. Co-administration of PEG-Hb (0.6 g/kg) with cisplatin produced significant tumor growth inhibition and pro-apoptotic and anti-proliferative effects as compared to cisplatin alone. These suggest the evaluated PEG-Hb in this experiment has positive effects on cisplatin or cisplatin-based chemotherapy, and further work to optimize its application is warranted.