Lipoxin A4 and Its Analogue Suppress the Tumor Growth of Transplanted H22 in Mice: The Role of Antiangiogenesis
Lipoxin A4 and Its Analogue Suppress the Tumor Growth of Transplanted H22 in Mice: The Role of Antiangiogenesis
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DOI：
10.1158/1535-7163.mct-10-0173
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发表时间：
2010-08-01
影响因子：
5.7
通讯作者：
Chen, Xiaoping
中科院分区：
文献类型：
--
作者：
Chen, Ying;Hao, Hua;Chen, Xiaoping
肿瘤血管生成在肿瘤发生、发展和转移中起着重要作用。一些研究表明，脂氧素，内源性抗炎脂质介质，可能参与肿瘤血管生成，但其管理机制仍然是未知的。本研究观察了外源性脂氧素A（4）（LXA（4））对小鼠肝癌细胞系（H22）和荷瘤小鼠模型的作用。结果发现，在H22细胞中，LXA（4）抑制血管内皮生长因子的产生，并降低缺氧诱导因子-1 α的水平。此外，它的类似物，BML-111，阻断血管内皮生长因子的表达在血清和肿瘤切片从H22荷瘤小鼠。H&E染色和抗CD 34抗体免疫组化显示BML-111抑制肿瘤相关血管生成，而LXA（4）对原代培养的人脐静脉内皮细胞增殖无影响。BML-111也能抑制肿瘤生长。我们还发现BML-111在抑制肿瘤组织中巨噬细胞浸润的同时促进原位凋亡。本研究结果为LXA（4）通过抑制肿瘤相关血管生成抑制小鼠移植性H22肿瘤的生长提供了新的证据。Mol Cancer Ther; 9（8）; 2164-74. (C)2010年AACR。
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. Mol Cancer Ther; 9(8); 2164-74. (C) 2010 AACR.