Inhibition of pancreatic cancer-cell growth and metastasis in vivo by a pyrazole compound characterized as a cell-migration inhibitor by an in vitro chemotaxis assay.
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| Abstract |
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.
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| Authors | Shuichiro Okamoto, Kei Miyano, Tominari Choshi, Norihiko Sugisawa, Takashi Nishiyama, Rika Kotouge, Masahiro Yamamura, Masakiyo Sakaguchi, Rie Kinoshita, Nahoko Tomonobu, Naoki Katase, Kyo Sasaki, Sohji Nishina, Keisuke Hino, Koji Kurose, Mikio Oka, Hisako Kubota, Tomio Ueno, Toshihiro Hirai, Hideyo Fujiwara, Chikage Kawai, Masumi Itadani, Aya Morihara, Kouji Matsushima, Shiro Kanegasaki, Robert M Hoffman, Akira Yamauchi, Futoshi Kuribayashi |
| Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 155 Pg. 113733 (Nov 2022) ISSN: 1950-6007 [Electronic] France |
| PMID | 36271542 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved. |
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