Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an 71000, Shannxi Province, China.
Department of Obstetrics and Gynecology, Fourth Military Medical University, Xi'an 710032, Shannxi Province, China.
Aging (Albany NY). 2021 Feb 17;13(5):7166-7179. doi: 10.18632/aging.202574.
Raddeanin A (RA), an active triterpenoid saponin extracted from the regel, plays an essential role in the suppression of many malignancies. We aimed to investigate the effects and potential mechanisms of RA on cervical cancer (CC). RA was used to treat CC cell lines (Hela and c-33A) for 24 h and 48 h. Then, the invasion, migration and cell cycle distribution of these two cell lines with RA treatment were respectively detected by transwell, wound healing and flow cytometry. Results revealed that RA significantly inhibited the invasion, migration, promoted the cell cycle arrest and apoptosis of Hela and c-33A cells. Moreover, RA was confirmed to activate the Slit2/Robo1 signaling, and bioinformatics analysis and luciferase reporter assay verified that miR-224-3p could target Slit2. Additionally, miR-224-3p overexpression reversed the inhibitory effect of RA on invasion and migration of CC cells, and it also restored the promoting effects of RA on cell cycle arrest and apoptosis. Lastly, miR-224-3p-upregulation inactivated the expression of Slit2 and Robo1 in RA-treated Hela and c-33A cells. These findings demonstrated that RA inhibits proliferation, invasion, migration and promotes apoptosis of CC cells through miR-224-3p/Slit2/Robo1 signaling pathway, which might guide the future studies or treatment of this disease.
雷达苷 A(RA)是从独活中提取的一种具有活性的三萜皂苷,在抑制多种恶性肿瘤方面发挥着重要作用。本研究旨在探讨 RA 对宫颈癌(CC)的作用及其潜在机制。用 RA 处理 CC 细胞系(Hela 和 c-33A)24 h 和 48 h,然后通过 Transwell、划痕愈合和流式细胞术分别检测 RA 处理后这两种细胞系的侵袭、迁移和细胞周期分布。结果表明,RA 显著抑制了 Hela 和 c-33A 细胞的侵袭和迁移,促进了细胞周期阻滞和凋亡。此外,RA 被证实能激活 Slit2/Robo1 信号通路,生物信息学分析和荧光素酶报告基因实验证实 miR-224-3p 可以靶向 Slit2。此外,过表达 miR-224-3p 逆转了 RA 对 CC 细胞侵袭和迁移的抑制作用,也恢复了 RA 对细胞周期阻滞和凋亡的促进作用。最后,miR-224-3p 的上调使 RA 处理的 Hela 和 c-33A 细胞中 Slit2 和 Robo1 的表达失活。这些发现表明,RA 通过 miR-224-3p/Slit2/Robo1 信号通路抑制 CC 细胞的增殖、侵袭、迁移,并促进其凋亡,这可能为该疾病的未来研究或治疗提供指导。