Astragaloside IV inhibits cell proliferation of colorectal cancer cell lines through down-regulation of B7-H3.

Astragaloside IV showed a pivotal anti-cancer efficacy in multiple types of cancers and reversed chemoresistance in colorectal cancer (CRC). However, it remained unknown whether and how Astragaloside IV suppressed the progression of CRC. In the present study, we found that Astragaloside IV treatment significantly and dose-dependently reduced cell proliferation of CRC cell lines (SW620 and HCT116), whereas it showed no significant influence on the cell proliferation of normal colonic cells (FHC). Flow cytometry (FCM) analysis indicated that there was a significant cell cycle arrest in G0/G1 phase of SW620 cells and HCT116 cells which were treated with Astragaloside IV. The mRNA levels and protein levels of several key cell cycle relative proteins (cyclin D1 and CDK4) were also dramatically decreased during the process of G0/G1 arrest after the administration of Astragaloside IV. In addition, we observed an obvious decrease of B7-H3 protein level upon Astragaloside IV treatment, which was a result of mRNA reduction that was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and CHX chase. We further identified that Astragaloside IV suppressed B7-H3 expression by elevating the expression of miR-29c level. Inhibition of miR-29c could dramatically reverse Astragaloside IV-induced B7-H3 decrease and cell growth arrest. This study suggests that Astragaloside IV is a promising anti-cancer drug in CRC.