Anticancer research · 2026
Establishment of Gemcitabine-resistant Mouse Pancreatic Ductal Adenocarcinoma Cell Line and Possible Therapeutic Agents.
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Miyashita Kumiko, Yamashita Kimihiro, Miyoshi Makoto, Nishiyama Takaaki, Ise Yuki, Ohsaka Shun, Shimizu Kazuya, Nishimura Noriyuki, Hori Yuichi
Аннотация
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 in vivo 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.
MATERIALS AND METHODS: Metastatic PDAC (mPDAC) cells, generated from CD133-positive pancreatic stem cells (mutant Trp53, Cdk4, Kras), were subjected to chronic in vivo 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.