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.
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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DOI：
10.1016/j.biopha.2022.113733
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发表时间：
2022-11
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通讯作者：
Shuichiro Okamoto;K. Miyano;T. Choshi;Norihiko Sugisawa;Takashi Nishiyama;Rika Kotouge;M. Yamamura;M. Sakaguchi;R. Kinoshita;Nahoko Tomonobu;N. Katase;Kyo Sasaki;S. Nishina;Keisuke Hino;K. Kurose;M. Oka;H. Kubota;T. Ueno;T. Hirai;H. Fujiwara;C. Kawai;Masumi Itadani;A. Morihara;K. Matsushima;S. Kanegasaki;R. Hoffman;Akira Yamauchi;F. Kuribayashi
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作者：
Shuichiro Okamoto;K. Miyano;T. Choshi;Norihiko Sugisawa;Takashi Nishiyama;Rika Kotouge;M. Yamamura;M. Sakaguchi;R. Kinoshita;Nahoko Tomonobu;N. Katase;Kyo Sasaki;S. Nishina;Keisuke Hino;K. Kurose;M. Oka;H. Kubota;T. Ueno;T. Hirai;H. Fujiwara;C. Kawai;Masumi Itadani;A. Morihara;K. Matsushima;S. Kanegasaki;R. Hoffman;Akira Yamauchi;F. Kuribayashi
胰腺癌难以治疗，因为它具有高度转移性和快速进展性。在使用名为 TAXIScan 的光学测定装置观察人胰腺 BxPC-3 细胞的行为时，我们发现几种合成的吡唑和嘧啶衍生物抑制细胞迁移。其中一种化合物 14-100 可以抑制荧光标记的 BxPC-3 细胞的转移，这些细胞被作为皮下生长的癌症碎片移植到裸鼠的胰腺中。令人惊讶的是，尽管其细胞毒性较低，但该化合物还显示出对体内癌细胞增殖的抑制作用，这表明该化合物改变了癌细胞原位生长所需的特征。单细胞 RNA 测序揭示了与转移、血管生成、炎症和上皮间质转化相关的基因表达变化。这些数据表明化合物14-100可能是抗胰腺癌的良好候选药物。
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 proliferationin vivo,suggesting that the compound alters cancer cell characteristics needed to growin situ. Single-cell RNA-sequencing revealed changes in gene expression associated with metastasis, angiogenesis, inflammation, and epithelial-mesenchymal transition. These data suggest that the compound14–100could be a good drug candidate against pancreatic cancer.