Baicalein mediates the anti-tumor activity in Osteosarcoma through lncRNA-NEF driven Wnt/β-catenin signaling regulatory axis.

BACKGROUND

Osteosarcoma (OS) is a common type of malignant bone tumor in adolescents with high risk of metastasis. However, the clinical management still remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely considered as an alternative treatment, and their extracts have proved to possess great potential for drug discovery. Baicalein (BA), the active pharmaceutical ingredient of , was proved to have anti-tumor properties in OS, but the mechanism remains poorly understood.

METHODS

The potential anti-cancer effects on cell growth, cell cycle, apoptosis and migration were examined in OS cells. Moreover, the lncRNA-Neighboring Enhancer of FOXA2 (lncRNA-NEF) and Wnt/β-catenin signaling were detected by qPCR and Western blotting assays. The effect of GA on tumor growth was investigated using a xenograft mice model.

RESULTS

In the present study, BA was found to significantly suppress tumor growth and And it was also found to inhibit the invasion and metastasis as well. As for the mechanism investigation, lncRNA-NEF was obviously upregulated by BA in OS cells, and thus induced the inactivation of Wnt/β-catenin signaling. Moreover, lncRNA-NEF knockdown partially reversed the BA-induced anti-cancer activities; and successfully compensated the suppressive effect on Wnt/β-catenin signaling. We therefore suggested that BA induced the inactivation of Wnt/β-catenin signaling through promoting lncRNA-NEF expression.

CONCLUSIONS

In conclude, our results demonstrated that BA suppressed tumor growth and metastasis and through an lncRNA-NEF driven Wnt/β-catenin regulatory axis, in which lncRNA-NEF was upregulated by BA, and thus induced the inactivation of Wnt/β-catenin signaling.

THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE

The findings derived from this study validates the anti-cancer activity of BA in OS and provides a novel underlying mechanism, which suggest that BA may be a potential candidate to develop the effective drug for OS patients.