Flavokawain C suppresses nephroblastoma growth by inducing autophagy-mediated downregulation of FABP4 via AMPK/mTOR pathway

Nephroblastoma is the most common pediatric kidney cancer. Flavokawain C (FKC) is a naturally occurring chalcone which has been reported to inhibit the growth of several cancers. However, whether FKC has therapeutic potential for nephroblastoma remains unclear. This study aimed to investigate the effect of FKC on nephroblastoma growth and reveal its possible mechanism. The viability, clone formation and proliferation of G401 cells under FKC treatment were evaluated by CCK-8, clone formation and EdU assays. The migration and invasion of G401 cells under FKC treatment were evaluated by transwell and wound healing assays. The effects of FKC on epithelial-mesenchymal transition (EMT) markers, autophagy-related proteins, FABP4 expression and AMPK/mTOR pathway were evaluated by western blot. The bioinformatic tools were used to evaluate the expression of in tumor tissues. Furthermore, the interaction between FKC and FABP4 in autophagy was analyzed by Co-IP assay. The in vivo assay was conducted to observe the effect of FKC on tumor growth. FKC was found to inhibit the viability, clone formation and proliferation of G401 cells. Then, FKC was found to exert an inhibitory effect on EMT, migration and invasion of G401 cells in vitro. Furthermore, FABP4 was overexpressed in nephroblastoma tissues, which was closely related to the prognosis of nephroblastoma patients. And FKC was found to suppress FABP4 expression by which affect the proliferation, migration and invasion of G401 cells. Moreover, AMPK/mTOR pathway was involved in the autophagy formation induced by FKC and mediated the degradation of FABP4. The in vivo study further confirmed that FKC inhibited the growth of nephroblastoma. This study demonstrates that FKC inhibits the proliferation, migration, and invasion of nephroblastoma cells by inducing AMPK pathway-mediated autophagy, leading to the degradation of FABP4.