What question did this study set out to answer?

The main aim is to create a gemcitabine-resistant model of pancreatic cancer to study resistance mechanisms.

March 29, 2026Open Access

Establishment of Gemcitabine-resistant Mouse Pancreatic Ductal Adenocarcinoma Cell Line and Possible Therapeutic Agents

Key Points

The main aim is to create a gemcitabine-resistant model of pancreatic cancer to study resistance mechanisms.
Developed metastatic PDAC cells from CD133-positive pancreatic stem cells with specific mutations.
Subjected cells to chronic gemcitabine selection to establish a resistant cell line (mPDAC-R).
Conducted transcriptomic profiling to identify genes associated with resistance.
mPDAC-R cells showed sustained growth and increased invasiveness under gemcitabine treatment.
Monoamine oxidase B (MAOB) was found to be significantly up-regulated.
Pharmacological inhibition of MAOB reduced proliferation and growth in gemcitabine-resistant and human PDAC cell lines.

Abstract

Background/Aim: Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to gemcitabine (GEM) resistance. This study aimed to establish a clinically relevant immunocompetent model to identify novel mediators of acquired GEM resistance. Materials and Methods: Metastatic PDAC (mPDAC) cells, generated from CD133-positive pancreatic stem cells (mutant Trp53, Cdk4, Kras), were subjected to chronic invivo GEM selection to establish a line with reduced sensitivity (mPDAC-R). Results: mPDAC-R exhibited sustained growth under GEM treatment, alongside enhanced invasiveness and metastatic potential. Transcriptomic profiling identified monoamine oxidase B (MAOB) as an up-regulated mediator. Pharmacological inhibition of MAOB significantly suppressed proliferation and tumor growth in both mPDAC-R and human PDAC cell lines. Conclusion: We established a novel GEM-resistant mPDAC model and identified MAOB as a promising therapeutic target. These findings provide a rationale for targeting MAOB-driven survival signals to overcome chemoresistance in refractory pancreatic cancer.

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