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. 2022 Feb 18;31:09636897221077921. doi: 10.1177/09636897221077921

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© The Author(s) 2022

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Figure 6. — Mechanism of action. MLN4924 treatment blocks neddylation by inactivation of NAE; yet, it also activates AKT and ERK pathways. Celecoxib downregulates the AKT and ERK, synergistically enhancing MLN4924-induced suppression of growth, survival, and EMT, and inducing apoptosis via Bcl2 signal pathways of UC cells. The combination of MLN4924 with celecoxib in vivo significantly suppresses the growth of UC by increasing the expression of caspase 3 and decreasing the expression of Ki67. NAE: NEDD8-activating enzyme; EMT: epithelial–mesenchymal transition; UC: urothelial carcinoma.