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Open Access Highly Accessed Research article

A novel oxygen carrier “YQ23” suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells

Chang Xian Li1, Bing L Wong2, Chang Chun Ling1, Yuen Yuen Ma1, Yan Shao1, Wei Geng1, Xiang Qi1, Sze Hang Lau2, Sui Yi Kwok2, Na Wei2, Fei Chuen Tzang2, Kevin TP Ng1, Xiao Bing Liu1, Chung Mau Lo1 and Kwan Man1*

Author Affiliations

1 Department of Surgery and Centre for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China

2 New B Innovation Limited, Hong Kong, China

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BMC Cancer 2014, 14:293  doi:10.1186/1471-2407-14-293

Published: 27 April 2014

Abstract

Background

Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. However, the high incidence of tumor metastasis after liver surgery remains a severe problem. We aim to investigate the roles and the underlying mechanism of YQ23, stabilized non-polymeric diaspirin cross-linked tetrameric hemoglobin, in liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury.

Methods

An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Major hepatectomy for tumor-bearing lobe and partial hepatic I/R injury were performed at two weeks after orthotopic liver tumor implantation. YQ23 (0.2 g/kg) was administered at 1 hour before ischemia and immediately after reperfusion. Blood samples were collected at day 0, 1, 7, 14, 21 and 28 for detection of circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs).

Results

Our results showed that YQ23 treatment effectively inhibited intrahepatic and lung metastases together with less tumor angiogenesis at 4 weeks after major hepatectomy and partial hepatic I/R injury. The levels of circulating EPCs and Tregs were significantly decreased in YQ23 treatment group. Furthermore, YQ23 treatment also increased liver tissue oxygenation during hepatic I/R injury. Up-regulation of HO1 and down-regulation of CXCR3, TNF-α and IL6 were detected after YQ23 treatment.

Conclusions

YQ23 treatment suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury in a rat liver tumor model through increasing liver oxygen and reducing the populations of circulating EPCs and Tregs.

Keywords:
YQ23; HCC; Tumor metastasis; Hepatic I/R injury; EPCs; Tregs