Lipoxin A4 and its analogue suppress the tumor growth of transplanted H22 in mice: the role of antiangiogenesis.
Tumor angiogenesis plays an essential role in carcinogenesis, cancer progression, and metastasis. Some studies indicate that lipoxins, endogenous anti-inflammatory lipid mediators, might be involved in tumor angiogenesis; however, the governing mechanisms are still unknown. In the present study, we examined the effects of exogenous lipoxin A(4) (LXA(4)) in mouse hepatocarcinoma cell line (H22) and H22-bearing mice model. It was found that in H22 cells, LXA(4) inhibited the production of vascular endothelial growth factor and reduced hypoxia-inducible factor-1 alpha level. In addition, its analogue, BML-111, blocked the expression of vascular endothelial growth factor in serum and tumor sections from H22-bearing mice. H&E staining and immunostaining with antibodies against CD34 revealed that BML-111 suppressed tumor-related angiogenesis in vivo, but LXA(4) could not influence the proliferation of primary cultured human umbilical vein endothelial cells. The tumor growth was also inhibited by BML-111. We also found that BML-111 enhanced the in situ apoptosis while inhibiting macrophage infiltration in tumor tissue. The results provide new evidence that LXA(4) suppresses the growth of transplanted H22 tumor in mice through inhibiting tumor-related angiogenesis.
Chen
Ying
Y
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei Province, China.
Hao
Hua
H
He
Songqing
S
Cai
Lei
L
Li
Yongsheng
Y
Hu
Shunze
S
Ye
Duyun
D
Hoidal
John
J
Wu
Ping
P
Chen
Xiaoping
X
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D020533:Angiogenesis Inhibitors; D006538:Heptanoic Acids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044045:Lipoxins; D042461:Vascular Endothelial Growth Factor A; C040527:lipoxin A4