Betulinic acid inhibits the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in human endometrial adenocarcinoma cells
Betulinic acid inhibits the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in human endometrial adenocarcinoma cells
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DOI：
10.1007/s11010-010-0395-8
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发表时间：
2010-07-01
影响因子：
4.3
通讯作者：
Palka, Jerzy A.
中科院分区：
文献类型：
--
作者：
Karna, Ewa;Szoka, Lukasz;Palka, Jerzy A.
尽管已知桦木酸（BA）可诱导肿瘤细胞凋亡和抗血管生成反应，但其作用的潜在机制尚不清楚。组织胶原代谢失调是肿瘤转化的后果之一。胶原蛋白降解的最后一步是由脯氨酸酶 [E.C.3.4.13.9] 介导的，它可能在血管生成中发挥作用。新血管的形成受缺氧诱导因子 1 (HIF-1) 的调节。 HIF-1 的表达与缺氧诱导的血管生成相关，血管生成是血管内皮细胞生长因子 (VEGF) 诱导的结果。由于 BA 具有抗癌活性，因此在培养的子宫内膜腺癌细胞 (EA) 中研究了其对胶原蛋白生物合成、HIF-1 α 和 VEGF 表达以及脯氨酸酶活性和表达的影响。结果发现，BA 抑制 EA 细胞中的胶原蛋白生物合成（5[H-3] 脯氨酸掺入测定）。在培养的人 EA 细胞中，伴随着脯氨酸酶活性和表达的平行降低，以及 α(1) 和 α(2) 整联蛋白、HIF-1 α 和 VEGF（蛋白质免疫印迹分析）表达的降低。数据表明，BA 可能通过抑制脯氨酸酶、HIF-1 α 和 VEGF 表达以及抑制胶原蛋白生物合成而具有抗血管生成潜力。
Although betulinic acid (BA) is known to induce apoptosis and antiangiogenic response in tumor cells, the underlying mechanism of its action is unknown. Deregulation of tissue collagen metabolism is one of the consequences of neoplastic transformation. The final step of collagen degradation is mediated by prolidase [E.C.3.4.13.9] which may play a role in angiogenesis. The formation of new blood vessels is regulated by the hypoxia-inducible factor 1 (HIF-1). The expression of HIF-1 correlates with hypoxia-induced angiogenesis as a result of the induction of vascular endothelial cell growth factor (VEGF). Since BA evokes anticancer activity, its effect on collagen biosynthesis, HIF-1 alpha and VEGF expressions, as well as prolidase activity and expression was studied in cultured endometrial adenocarcinoma (EA) cells. It was found that BA inhibits collagen biosynthesis in EA cells (5[H-3] proline incorporation assay). It was accompanied by a parallel decrease in prolidase activity and expression and decrease in expressions of alpha(1) and alpha(2) integrins, HIF-1 alpha, and VEGF (western immunoblot analysis) in cultured human EA cells. The data suggest that BA may have anti-angiogenic potential by inhibition of prolidase, HIF-1 alpha and VEGF expressions, and inhibition of collagen biosynthesis.