Berbamine inhibits cell proliferation and invasion by increasing FTO expression in renal cell carcinoma cells.

Abstract

Background: Berbamine (BBM) has been reported to play an important role in the anti-inflammatory and anti-neoplastic activities. However, whether BBM mediates the anti-tumor efficacy in renal cell carcinoma (RCC) cells and the potential molecular mechanisms remain unclear.

Methods: The effects of BBM on the proliferation, colony formation, cell cycle, cell migration and invasion abilities were performed in RCC cells 786-O and OSRC2, and the effect of BBM on tumor formation was further explored. Furthermore, the effects of BBM on the expression of fat mass and obesity associated gene (FTO) and its target genes were investigated. Finally, the effects of BBM on the proliferation, and invasion of RCC cells after knockdown of FTO were detected.

Results: BBM effectively inhibited the proliferation, migration and invasion of RCC cells in a dose-dependent manner, and BBM also significantly inhibited the growth of tumor in vivo, which has fewer toxic effects on the other organs. Molecular mechanistic studies showed that BBM significantly promoted the expression of FTO mRNA and protein in RCC cells, and knock-down of FTO by siRNA transfection reversed the inhibitory effect of BBM on the growth and invasion of RCC cells.

Conclusion: Collectively, our findings revealed that targeting the tumor suppressive FTO by BBM is a new option to inhibit RCC cells growth and metastasis, providing a good drug candidate potential for development novel therapeutics against metastatic RCC.