FOXN3 attenuates doxorubicin resistance of bladder urothelial carcinoma via SIRT6/PI3K/AKT/mTOR pathway

Purpose: To investigate the effect of forkhead box N3 (FOXN3) protein on doxorubicin (DOX) resistance urothelial carcinoma (BLCA).
 Methods: Bioinformatics prediction and immunoblotting were used to evaluate FOXN3 expression in BLCA tissues cells. The overexpression was achieved by cell transfection. effects DOX apoptosis determined immunoblotting, assay, flow cytometry, while applied SIRT6/PI3K/AKT/mTOR signaling activity. Finally, SIRT6 exogenous addition a PI3K/AKT activator molecular mechanism which regulates phenotype.
 Results: downregulated DOX-resistant cells its attenuated (p < 0.01). Furthermore, apoptotic ratio increased from 7.54 26.83 % J82/DOX 6.31 17.89 T24/DOX 0.01) after overexpression. Moreover, upregulation inhibited sirtuin 6 (SIRT6) inactivated PI3K/AKT/mTOR pathway. Both activation abrogated FOXN3-mediated inhibition cells.
 Conclusion: attenuates through pathway, thus providing promising therapeutic strategy for management BLCA.