DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors.

ABSTRACT: Objective: Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer (NSCLC), but no direct Mcl-1 inhibitor is currently available for clinical use. Thus, novel therapeutic strategies are urgently needed to target Mcl-1 and sensitize the anti-NSCLC activity of Bcl-2 inhibitors. Methods: Cell proliferation was measured using sulforhodamine B and colony formation assays, and apoptosis was detected with Annexin V-FITC staining. Gene expression was manipulated using siRNAs and plasmids. Real-time PCR and Western blot were used to measure mRNA and protein levels. Immunoprecipitation and immunofluorescence were used to analyze co-localization of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) and Mcl-1. Results:

SUBMITTER: Li Y 

PROVIDER: S-EPMC7309455 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature