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Biomed Pharmacother ; 155: 113733, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271542

RESUMO

Pancreatic cancer is recalcitrant to treatment as it is highly metastatic and rapidly progressive. While observing the behavior of human pancreatic BxPC-3 cells using an optical assay device called TAXIScan, we found that several synthetic pyrazole and pyrimidine derivatives inhibited cell migration. One such compound, 14-100, inhibited metastasis of fluorescence-labeled BxPC-3 cells, which were transplanted into the pancreas of nude mice as a subcutaneously grown cancer fragment. Surprisingly, despite its low cytotoxicity, the compound also showed an inhibitory effect on cancer cell proliferation in vivo, suggesting that the compound alters cancer cell characteristics needed to grow in situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound 14-100 could be a good drug candidate against pancreatic cancer.


Assuntos
Quimiotaxia , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , Camundongos Nus , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Pancreáticas/patologia , Pâncreas/patologia , Transformação Celular Neoplásica , Pirazóis/farmacologia , Pirazóis/uso terapêutico , RNA , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Neoplasias Pancreáticas
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