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

Chang Xian Li,Xiao Bing Liu,Chang Chun Ling,Yuen Yuen Ma,Xiang Qi,Fei Chuen Tzang,Wei Geng,Bing L Wong,Na Wei,Sze Hang Lau,Kwan Man,Kevin Tp Ng,Chung Mau Lo,Yan Shao,Sui Yi Kwok

doi:10.1186/1471-2407-14-293

Chang Xian Li, Xiao Bing Liu + Show 13 more

Open Access

https://doi.org/10.1186/1471-2407-14-293

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Abstract

BackgroundSurgical 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.MethodsAn 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).ResultsOur 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.ConclusionsYQ23 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.

Highlights

Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients
We aimed to investigate whether the treatment of YQ23 can suppress liver tumor metastasis after major hepatectomy and partial hepatic ischemia reperfusion (I/R) injury by increasing liver oxygen and reducing circulating endothelial progenitor cells (EPCs) and Tregs levels in an orthotopic rat liver tumor model
YQ23 suppressed liver tumor metastasis after major hepatectomy and partial hepatic I/R injury In order to investigate the effect of YQ23 on the metastasis of liver tumor after liver surgery, we established a rat orthotopic liver tumor model with local and distant metastatic potentials

Summary

Introduction

Surgical therapies are the first-line treatments for hepatocellular carcinoma (HCC) patients. The high incidence of tumor metastasis after liver surgery remains Surgical stress injury such as liver ischemia and hypoxia are inevitable consequence during liver surgery. Accumulating evidence suggested that tissue ischemia and hypoxia can rapidly increase the number of circulating EPCs and Tregs [4,5,6]. These events are associated with elevated levels of hypoxia inducible factor-1α (HIF1α) responsive chemokines and inflammatory cytokines/ chemokines that stimulate the release and recruitment of EPCs and Trges from the bone marrow [4,6,7,8,9,10]. It has been found that increased numbers of Tregs are detected in peripheral blood of cancer patients and accumulate in tumor regions [16,17,18]

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