Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival
Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival
复制标题
熊果酸对人子宫内膜异位基质细胞存活的抑制作用
DOI：
10.1159/000502258
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发表时间：
2019-09
影响因子：
2.1
通讯作者：
Xiaoyan Liang
中科院分区：
文献类型：
--
作者：
Jingjie Li;Zhi Zeng;Yajie Chang;Manchao Li;Qiuli Wu;Pan Chen;Xiaoyan Liang
背景/目的：需要鉴定用于子宫内膜异位症治疗的新候选化合物。环加氧酶-2 (COX-2) 被认为是控制子宫内膜异位症进展和复发的关键靶点。在这里，我们确定熊果酸 (UA) 是 COX-2 的天然抑制剂，并研究其对子宫内膜异位症进展的影响。方法：将从子宫内膜异位症患者中分离的原代人子宫内膜异位基质细胞暴露于浓度为 15、30、45 和 60 μM 的 UA。进行 3-(4,5-二甲基噻嗪唑-2-基)-2,5-二苯基四唑溴化物测定、5'-溴-2'-脱氧尿苷测定和 Caspase-3 活性测量来检测细胞生长和凋亡。采用酶联免疫吸附测定法检测COX-2和血管内皮生长因子（VEGF）蛋白表达以及前列腺素E2（PGE2）水平。还使用人脐静脉内皮细胞进行毛细管形成测定以确定血管生成。结果：UA 显着降低细胞活力，抑制增殖，并以剂量依赖性方式增加 caspase-3 活性。 UA 降低了 COX-2 蛋白表达和随后的 PGE2 产生。同时，UA暴露减少了基质细胞中VEGF的分泌，毛细管形成实验证实了UA对血管生成的抑制作用。此外，UA 增加了 c-Jun N 末端激酶和 p38 的磷酸化。结论：我们的数据表明，UA 作为 COX-2 的天然抑制剂，通过抑制增殖和血管生成并促进细胞凋亡来控制人子宫内膜异位基质细胞的存活。
Background/Aims: The identification of new compound candidates for endometriosis treatment is needed. Cyclooxygenase-2 (COX-2) is considered a crucial target to control the progress and recurrence of endometriosis. Here, we identified ursolic acid (UA) as a natural inhibitor of COX-2 and investigated its effects on endometriosis progression. Methods: Primary human endometriotic stromal cells isolated from patients with endometriosis were exposed to UA at concentrations of 15, 30, 45, and 60 μM. 3-(4,5-Dimethylthiaziazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, 5′-bromo-2’-deoxy-uridine assays, and Caspase-3 activity measurements were performed to detect cell growth and apoptosis. Enzyme-linked immunosorbent assays were used to detect COX-2 and vascular endothelial growth factor (VEGF) protein expression and prostaglandin E2 (PGE2) levels. Capillary-tubule formation assays using human umbilical vein endothelial cells were also carried out to determine angiogenesis. Results: UA significantly decreased cell viability, inhibited proliferation, and increased caspase-3 activity in a dose-dependent manner. COX-2 protein expression and the subsequent PGE2 production were both reduced by UA. Meanwhile, UA exposure decreased VEGF secretion in the stromal cells and the capillary-tubule formation assay confirmed the inhibitory effect of UA on angiogenesis. Furthermore, UA increased the phosphorylation of c-Jun N-terminal kinase and p38. Conclusions: Our data suggest that UA plays a role as a natural inhibitor of COX-2 to control the survival of human endometriotic stromal cells by inhibiting proliferation and angiogenesis and promoting apoptosis.
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DOI：
10.1210/jcem.86.12.8082
发表时间：
2001-12
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
S. Tsai;Meng-Hsing Wu;Chen-Chung Lin;H. Sun;H. Chen
通讯作者：
S. Tsai;Meng-Hsing Wu;Chen-Chung Lin;H. Sun;H. Chen
影响因子：
6.7
作者：
L. Yuan;Fanghua Shen;Yuan Lu;Xi-shi Liu;Sun-Wei Guo
通讯作者：
L. Yuan;Fanghua Shen;Yuan Lu;Xi-shi Liu;Sun-Wei Guo
影响因子：
4.3
作者：
D. Graham;D. Campen;R. Hui
通讯作者：
D. Graham;D. Campen;R. Hui
影响因子：
6.1
作者：
Meresman, GF;Bilotas, MA;Barañao, RI
通讯作者：
Barañao, RI
DOI：
10.1016/j.ejogrb.2006.04.008
发表时间：
2007-05-01
期刊：
EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY
影响因子：
--
作者：
Szymanowski, Krzysztof
通讯作者：
Szymanowski, Krzysztof