Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.
Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.
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Triptolide通过阻断刺猬/GLI途径来抑制上皮卵巢肿瘤的生长。
DOI：
10.18632/aging.205110
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发表时间：
2023-10-17
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影响因子：
--
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上皮性卵巢癌(EOC)是卵巢癌(OC)中最主要的亚型，预后差，侵袭性强。雷公藤甲素(TPL)和其他中草药一样，在现代医学中发挥着重要的作用。基于Gli依赖的荧光素酶报告活性的筛选体系评估了800多种天然药材对HH信号通路活性的影响，发现TPL对HH信号通路活性具有良好的抑制作用。然而，TPL参与调节HH途径的意义和机制还没有得到很好的探索。因此，本工作旨在更好地了解TPL如何影响HH途径的活性，进而影响EOC的生物学行为。我们的发现观察到，Smo激动剂SAG诱导的EOC细胞的增殖、迁移和侵袭被TPL以浓度依赖的方式显著逆转。进一步的证据表明，TPL通过依赖Gli1和Gli2泛素化来促进Gli1和Gli2的降解，从而抑制HH信号通路的活性。我们的体内研究也证实了TPL对EOC的生长有明显的抑制作用。综上所述，我们的结果表明，TPL的抗肿瘤机制之一是靶向抑制HH/Gli途径。
Epithelial ovarian cancer (EOC), the most predominant subtype of ovarian cancer (OC), involves poor prognosis and exhibits high aggression. Triptolide (TPL), like other Chinese herbs, has historically played a significant role in modern medicine. The screening system based on Gli-dependent luciferase reporter activity assessed the effects of over 800 natural medicinal materials on hedgehog (Hh) signaling pathway activity and discovered that TPL had an excellent inhibitory effect on Hh signaling pathway activity. However, the significance and mechanism of TPL involvement in regulating the Hh pathway have not been well explored. Thus, this work aimed to understand better how TPL affects the Hh pathway activity, which, in turn, influences the biological behavior of EOC. Our findings observed that Smo agonist SAG-induced EOC cell proliferation, migration, and invasion were drastically reversed by TPL in a concentration-dependent pattern. Further evidence suggested that TPL promotes the degradation of Gli1 and Gli2 to inhibit the activity of the Hh signaling pathway by relying on Gli1 and Gli2 ubiquitination. Our in vivo studies also confirmed that TPL could significantly inhibit the tumor growth of EOC. Taken together, our results revealed that one of the antitumor mechanisms of TPL was the targeted inhibition of the Hh/Gli pathway.
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DOI：
10.1038/nrclinonc.2013.5
发表时间：
2013-04
期刊：
Nature reviews. Clinical oncology
影响因子：
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DOI：
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发表时间：
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影响因子：
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