Li Chang Xian, Wong Bing L, Ling Chang Chun, Ma Yuen Yuen, Shao Yan, Geng Wei, Qi Xiang, Lau Sze Hang, Kwok Sui Yi, Wei Na, Tzang Fei Chuen, Ng Kevin T P, Liu Xiao Bing, Lo Chung Mau, Man Kwan
Department of Surgery and Centre for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
BMC Cancer. 2014 Apr 27;14:293. doi: 10.1186/1471-2407-14-293.
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.
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).
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.
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.
手术治疗是肝细胞癌（HCC）患者的一线治疗方法。然而，肝切除术后肿瘤转移的高发生率仍然是一个严重问题。我们旨在研究稳定的非聚合双阿司匹林交联四聚体血红蛋白YQ23在肝大部切除和部分肝缺血再灌注（I/R）损伤后肝肿瘤转移中的作用及潜在机制。
使用肝癌细胞系McA-RH7777在布法罗大鼠中建立原位肝肿瘤模型。在原位肝肿瘤植入两周后，对荷瘤叶进行肝大部切除术并造成部分肝I/R损伤。在缺血前1小时和再灌注后立即给予YQ23（0.2 g/kg）。在第0、1、7、14、21和28天采集血样，检测循环内皮祖细胞（EPCs）和调节性T细胞（Tregs）。
我们的结果表明，YQ23治疗在肝大部切除和部分肝I/R损伤后4周有效抑制肝内和肺转移，同时肿瘤血管生成减少。YQ23治疗组循环EPCs和Tregs水平显著降低。此外，YQ23治疗还增加了肝I/R损伤期间的肝组织氧合。YQ23治疗后检测到HO1上调，CXCR3、TNF-α和IL6下调。
在大鼠肝肿瘤模型中，YQ23治疗通过增加肝脏氧含量并减少循环EPCs和Tregs数量，抑制了肝大部切除和部分肝I/R损伤后的肝肿瘤转移。
