Enhancement of cisplatin-based TACE by a hemoglobin-based oxygen carrier in an orthotopic rat HCC model. (August 2014)

• Record Type: Journal Article
• Authors: Liu, Xiao-Bing; Cheng, Qiao; Geng, Wei; Ling, Chang-Chun; Liu, Yan; Ng, Kevin Tak-Pan; Yam, Judy Wai-Ping; Guan, Xin-Yuan; Lo, Chung-Mau; Man, Kwan
• Is Part Of: Artificial cells, nanomedicine, and biotechnology. Volume 42:Number 4(2014:Aug.)
• Page Start: 229
• Page End: 236
• Publication Date: 2014-08
• Subjects: Artificial cells -- Periodicals; Nanotechnology -- Periodicals; Blood substitutes -- Periodicals; Tissue engineering -- Periodicals; Molecules -- Periodicals; Biotechnology -- Periodicals; 615.39
• DOI: 10.3109/21691401.2013.808647
• Languages: English
• ISSNs: 2169-1401

Abstract

<abstract> <title>Abstract</title> <p> <italic>Objective:</italic> Hypoxic tumor cells are more resistant to standard chemotherapies. A number of studies indicated that improving oxygenation inside the tumor could serve as a potential strategy to target hypoxia-induced chemoresistance. In this study, we examined whether a hemoglobin-based oxygen carrier (OC89) could increase tumor oxygenation and thus enhance the efficiency of transarterial chemoembolization (TACE) in an orthotopic rat HCC model. <italic>Methods:</italic> Efficiency of the hemoglobin-based oxygen carrier (OC89) in improving tumor oxygenation was examined by OxyLab pO<sub>2</sub>. Sensitization of chemotherapy (cisplatin) in TACE by OC89 was evaluated in four different therapeutic regimens including cisplatin (1 mg/kg) + OC89 (0.2 g/kg), cisplatin (1 mg/kg) + OC89 (0.4 g/kg), cisplatin (3 mg/kg) + OC89 (0.2 g/kg), cisplatin (3 mg/kg) + OC89 (0.4 g/kg). For all the therapeutic regimens, a single delivery of OC89 via the tail vein was performed 1 h before TACE. <italic>Results:</italic> Compared with Ringer's buffer, systemic delivery of OC89 (0.4 g/kg) attenuated tumor hypoxia (<italic>p</italic> < 0.05). Additionally, partial pressure of oxygen (pO<sub>2</sub>) fraction of low readings (0–10 mmHg) inside the tumor decreased from 74.1% to 24.6% after OC89 delivery, while pO<sub>2</sub> fraction of high readings (15–25 mmHg) increased from 22.2% to 41.5%. When cisplatin was combined with OC89, regimen cisplatin (3 mg/kg) + OC89 (0.4 g/kg) resulted in a significant inhibition of tumor growth at Day 21 after therapy (<italic>p</italic> < 0.05). Further investigation indicated that OC89 delivery influenced anti-apoptotic and pro-apoptotic balance of the UPR pathway in the tumor. <italic>Conclusions:</italic> Our data suggest that targeting tumor hypoxia with the hemoglobin-based O<sub>2</sub> carrier serves as a promising approach to enhance the efficacy of cisplatin-based chemotherapy in HCC.</p> </abstract>