Raddeanin A inhibits proliferation, invasion, migration and promotes apoptosis of cervical cancer cells via regulating miR-224-3p/Slit2/Robo1 signaling pathway

Abstract

Raddeanin A (RA), an active triterpenoid saponin extracted from the Anemone raddeana 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.