Article Sidebar
Published:
Feb 13, 2023Keywords:
Article Details
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.
Main Article Content
FOXN3 attenuates doxorubicin resistance of bladder urothelial carcinoma via SIRT6/PI3K/AKT/mTOR pathway
Abstract
Purpose: To investigate the effect of forkhead box N3 (FOXN3) protein on doxorubicin (DOX) resistance of urothelial carcinoma (BLCA).
Methods: Bioinformatics prediction and immunoblotting were used to evaluate FOXN3 expression in BLCA tissues and cells. The FOXN3 overexpression was achieved by cell transfection. The effects of FOXN3 on DOX resistance and cell apoptosis were determined by immunoblotting, DOX resistance assay, and flow cytometry, while immunoblotting was applied to evaluate SIRT6/PI3K/AKT/mTOR signaling activity. Finally, SIRT6 overexpression and exogenous addition of a PI3K/AKT activator were used to investigate the molecular mechanism by which FOXN3 regulates DOX resistance phenotype.
Results: The FOXN3 was downregulated in DOX-resistant BLCA tissues and cells while its overexpression attenuated doxorubicin resistance (p < 0.01). Furthermore, apoptotic cell ratio increased from 7.54 to 26.83 % in J82/DOX cells and from 6.31 to 17.89 % in T24/DOX cells (p < 0.01) after FOXN3 overexpression. Moreover, FOXN3 upregulation inhibited sirtuin 6 (SIRT6) expression and inactivated PI3K/AKT/mTOR signaling pathway. Both SIRT6 overexpression and PI3K/AKT activation abrogated the FOXN3-mediated inhibition of DOX resistance in BLCA cells.
Conclusion: The FOXN3 attenuates the DOX resistance of BLCA through SIRT6/PI3K/AKT/mTOR pathway, thus providing a promising therapeutic strategy for the management of BLCA.
