A novel oxygen carrier "YQ23" suppresses the liver tumor metastasis by decreasing circulating endothelial progenitor cells and regulatory T cells.
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.
Chang Xian
CX
Li
Bing L
BL
Wong
Chang Chun
CC
Ling
Yuen Yuen
YY
Ma
Yan
Y
Shao
Wei
W
Geng
Xiang
X
Qi
Sze Hang
SH
Lau
Sui Yi
SY
Kwok
Na
N
Wei
Fei Chuen
FC
Tzang
Kevin T P
KT
Ng
Xiao Bing
XB
Liu
Chung Mau
CM
Lo
Department of Surgery and Centre for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. kwanman@hkucc.hku.hk.
Kwan
K
Man
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D045744:Cell Line, Tumor; D066026:Endothelial Progenitor Cells / Q000187:drug effects; D006454:Hemoglobins / Q000008:administration & dosage*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D009360:Neoplastic Cells, Circulating; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000601:surgery; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D006454:Hemoglobins; C000595252:YQ23 compound; D010100:Oxygen