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Fig. 3 | Journal of Hematology & Oncology

Fig. 3

From: Cyclin D1-CDK4 activity drives sensitivity to bortezomib in mantle cell lymphoma by blocking autophagy-mediated proteolysis of NOXA

Fig. 3

Autophagy inhibitors potentiate bortezomib-induced cell death through NOXA stabilization. a Co-treatment of bortezomib with an autophagy inhibitor potentiates half-life increase of NOXA protein. MCL cell line Jeko-1 was treated with 2 mM 3-MA for 16 h and subsequently co-treated with 7 nM bortezomib. After 14 h, 20 μg/ml cycloheximide was added to the cells and samples were harvested 0, 30, 45, 60, 90, and 120 min after cycloheximide exposition for Western blot analysis (upper panel) and corresponding densitometric analysis of NOXA protein stability (lower panel). b Co-treatment of Bortezomib with autophagy inhibitors potentiates cell death induction as well as NOXA protein accumulation. MCL cell line Jeko-1 was treated with 20 μM liensinine, 40 μM hydroxychloroquine, or 2 mM 3-MA for 16 h and subsequently co-treated with 8 nM bortezomib. After 8 h, protein expression was analyzed (upper panel), and after 24 h treatment, cell death was assessed by AnnexinV-PI staining (lower panel). Data represent means ± S.D. from three independent experiments

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