Knockdown of NUPR1 Enhances the Sensitivity of Non-small-cell Lung Cancer Cells to Metformin by AKT Inhibition.

Abstract

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.

• Authors: Yu Jin Kim, Sung-Eun Hong, Se-Kyeong Jang, Ki Soo Park, Chun-Ho Kim, In-Chul Park, Hyeon-Ok Jin
• Journal: Anticancer research (Anticancer Res) Vol. 42 Issue 7 Pg. 3475-3481 (Jul 2022) ISSN: 1791-7530 [Electronic] Greece
• PMID: 35790270 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Activating Transcription Factor 4
• Metformin
• Proto-Oncogene Proteins c-akt

Topics

• Activating Transcription Factor 4
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics)
• Diabetes Mellitus, Type 2
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Metformin (pharmacology)
• Proto-Oncogene Proteins c-akt (genetics)