TY - JOUR
T1 - 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
AU - Okamoto, Shuichiro
AU - Miyano, Kei
AU - Choshi, Tominari
AU - Sugisawa, Norihiko
AU - Nishiyama, Takashi
AU - Kotouge, Rika
AU - Yamamura, Masahiro
AU - Sakaguchi, Masakiyo
AU - Kinoshita, Rie
AU - Tomonobu, Nahoko
AU - Katase, Naoki
AU - Sasaki, Kyo
AU - Nishina, Sohji
AU - Hino, Keisuke
AU - Kurose, Koji
AU - Oka, Mikio
AU - Kubota, Hisako
AU - Ueno, Tomio
AU - Hirai, Toshihiro
AU - Fujiwara, Hideyo
AU - Kawai, Chikage
AU - Itadani, Masumi
AU - Morihara, Aya
AU - Matsushima, Kouji
AU - Kanegasaki, Shiro
AU - Hoffman, Robert M.
AU - Yamauchi, Akira
AU - Kuribayashi, Futoshi
N1 - Funding Information:
We would like to thank Mr. Naoki Honji for advice on this study, Professor Lars Ivo Partecke for kindly providing PAN02 cell line, Editage (www.editage.jp) for English language editing, and the Central Research Center of Kawasaki Medical School for technical supports.
Publisher Copyright:
© 2022 The Authors
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - Chemotaxis
KW - Gemcitabine
KW - Pancreatic cancer
KW - Pyrazole
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U2 - 10.1016/j.biopha.2022.113733
DO - 10.1016/j.biopha.2022.113733
M3 - Article
C2 - 36271542
AN - SCOPUS:85139076258
SN - 0753-3322
VL - 155
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 113733
ER -
