PT - JOURNAL ARTICLE AU - YU JIN KIM AU - SUNG-EUN HONG AU - SE-KYEONG JANG AU - KI SOO PARK AU - CHUN-HO KIM AU - IN-CHUL PARK AU - HYEON-OK JIN TI - Knockdown of NUPR1 Enhances the Sensitivity of Non-small-cell Lung Cancer Cells to Metformin by AKT Inhibition AID - 10.21873/anticanres.15834 DP - 2022 Jul 01 TA - Anticancer Research PG - 3475--3481 VI - 42 IP - 7 4099 - http://ar.iiarjournals.org/content/42/7/3475.short 4100 - http://ar.iiarjournals.org/content/42/7/3475.full SO - Anticancer Res2022 Jul 01; 42 AB - Background/Aim: Metformin is a widely used drug for type 2 diabetes mellitus and has recently attracted broad attention for its therapeutic effects on many cancers. This study aimed to investigate the molecular mechanism of metformin’s anticancer activity. Materials and Methods: Cell viability was measured by MTT assay. Gene and protein expression levels were determined by reverse transcription-polymerase chain reaction and western blot analyses, respectively. Results: Metformin and phenformin markedly induced NUPR1 expression in a dose- and time-dependent manner in H1299 non-small-cell lung cancer (NSCLC) cells. The silencing of NUPR1 in H1299 NSCLC cells enhanced cell sensitivity to metformin or ionizing radiation. Our previous report showed that metformin induces AKT serine/threonine kinase (AKT) activation in an activating transcription factor 4 (ATF4)-dependent manner and that the inhibition of AKT promotes cell sensitivity to metformin in H1299 NSCLC cells. Interestingly, ATF4-induced AKT activation in H1299 NSCLC cells treated with metformin was suppressed by the knockdown of NUPR1. Conclusion: Targeting NUPR1 could enhance the sensitivity of H1299 NSCLC cells to metformin by AKT inhibition.