Ailanthone Restrains Osteosarcoma Growth and Metastasis by Decreasing the Expression of Regulator of G Protein Signaling 4 and Twist Family BHLH Transcription Factor 1

Abstract

Traditional Chinese medicine Ailanthone (AIL) has been confirmed to possess antimalarial, anti-inflammatory, and anticancer effects. Here, this study aimed to excavate the biological role and mechanism of AIL on osteosarcoma (OS) progression. Levels of Regulator of G protein signaling 4 (RGS4) and Twist Family BHLH Transcription Factor 1 (TWIST1) were detected by qRT-PCR and western blotting. In vitro and tumor formation experiments were conducted for functional analysis. The protein interaction between RGS4 and TWIST1 was verified by using a Co-immunoprecipitation assay. AIL impeded the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression, but induced apoptosis in OS cells. RGS4 was highly expressed in OS tissues and cells and was decreased by AIL in cells. RGS4 silencing suppressed the growth and metastasis of OS cells, and RGS4 overexpression reversed the anticancer action of AIL in OS cells. Mechanistically, RGS4 interacted with TWIST1 and positively regulated its expression. TWIST1 was highly expressed in OS tissues and cells and could be reduced by AIL in cells. Moreover, TWIST1 overexpression abolished RGS4 silencing-triggered growth and metastasis inhibition in OS cells. Importantly, AIL impeded OS growth and metastasis in vivo by regulating RGS4 and TWIST1. Ailanthone restrained OS growth and metastasis by decreasing RGS4 and TWIST1 expression.