AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.
Humans
Phosphatidylinositol 3-Kinases
/ metabolism
Growth Inhibitors
/ pharmacology
Pancreatic Neoplasms
/ pathology
Antineoplastic Agents
/ pharmacology
Carcinoma, Pancreatic Ductal
/ pathology
Gemcitabine
TOR Serine-Threonine Kinases
Protein Kinase Inhibitors
/ pharmacology
Phosphoinositide-3 Kinase Inhibitors
/ pharmacology
Cell Proliferation
Cell Line, Tumor
Pancreatic Neoplasms
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
04
05
2023
accepted:
24
10
2023
medline:
13
11
2023
pubmed:
9
11
2023
entrez:
9
11
2023
Statut:
epublish
Résumé
Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy.
Identifiants
pubmed: 37943821
doi: 10.1371/journal.pone.0294065
pii: PONE-D-23-13615
pmc: PMC10635512
doi:
Substances chimiques
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Growth Inhibitors
0
Antineoplastic Agents
0
Gemcitabine
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Protein Kinase Inhibitors
0
Phosphoinositide-3 Kinase Inhibitors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0294065Informations de copyright
Copyright: © 2023 Ingle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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