Linagliptin decreased the tumor progression on glioblastoma model

Shohei Tsuji; Urara Kudo; Ryo Hatakeyama; Kenji Shoda; Shinsuke Nakamura; Masamitsu Shimazawa

doi:10.1016/j.bbrc.2024.149897

Linagliptin decreased the tumor progression on glioblastoma model

Biochem Biophys Res Commun. 2024 Jun 4:711:149897. doi: 10.1016/j.bbrc.2024.149897. Epub 2024 Apr 9.

Authors

Shohei Tsuji¹, Urara Kudo¹, Ryo Hatakeyama¹, Kenji Shoda², Shinsuke Nakamura¹, Masamitsu Shimazawa³

Affiliations

¹ Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
² Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan; Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
³ Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: shimazawa@gifu-pu.ac.jp.

PMID: 38608433
DOI: 10.1016/j.bbrc.2024.149897

Abstract

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic drugs and are used for type II diabetes. Previous studies showed that DPP-4 expression is observed in several tumor types and DPP-4 inhibitors suppress the tumor progression on murine tumor models. In this study, we evaluated the role of DPP-4 and the antitumor effect of a DPP-4 inhibitor, linagliptin, on glioblastoma (GBM).

Methods: We analyzed DPP-4 expression in glioma patients by the public database. We also analyzed DPP-4 expression in GBM cells and the murine GBM model. Then, we evaluated the cell viability, cell proliferation, cell migration, and expression of some proteins on GBM cells with linagliptin. Furthermore, we evaluated the antitumor effect of linagliptin in the murine GBM model.

Results: The upregulation of DPP-4 expression were observed in human GBM tissue and murine GBM model. In addition, DPP-4 expression levels were found to positively correlate with the grade of glioma patients. Linagliptin suppressed cell viability, cell proliferation, and cell migration in GBM cells. Linagliptin changed the expression of phosphorylated NF-kB, cell cycle, and cell adhesion-related proteins. Furthermore, oral administration of linagliptin decreases the tumor progression in the murine GBM model.

Conclusion: Inhibition of DPP-4 by linagliptin showed the antitumor effect on GBM cells and the murine GBM model. The antitumor effects of linagliptin is suggested to be based on the changes in the expression of several proteins related to cell cycle and cell adhesion via the regulation of phosphorylated NF-kB. This study suggested that DPP-4 inhibitors could be a new therapeutic strategy for GBM.

Keywords: Dipeptidyl peptidase-4 (DPP-4); Glioblastoma (GBM); Linagliptin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Brain Neoplasms* / drug therapy
Brain Neoplasms* / metabolism
Brain Neoplasms* / pathology
Cell Line, Tumor
Cell Movement* / drug effects
Cell Proliferation* / drug effects
Cell Survival / drug effects
Dipeptidyl Peptidase 4* / metabolism
Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
Disease Progression*
Glioblastoma* / drug therapy
Glioblastoma* / metabolism
Glioblastoma* / pathology
Humans
Linagliptin* / pharmacology
Linagliptin* / therapeutic use
Male
Mice

Substances

Linagliptin
Dipeptidyl-Peptidase IV Inhibitors
Dipeptidyl Peptidase 4
Antineoplastic Agents
DPP4 protein, human