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樟脑酰胺B通过抑制Smad/FAK/Akt轴并促进Snail/BMP4复合物的降解来抑制人结肠癌细胞的转移。

Camphorataimide B suppresses the metastasis of human colorectal cancer cell by inhibiting Smad/FAK/Akt axis and promoting degradation of Snail/BMP4 complex.

作者信息

Huang Chi-Chou, Hung Chia-Hung, Lee Yi-Ju, Tseng Tsui-Hwa, Lee Yean-Jang, Kao Shao-Hsuan, Wang Chau-Jong

机构信息

Department of Colorectal Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan.

School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

J Food Drug Anal. 2022 Jun 15;30(2):271-282. doi: 10.38212/2224-6614.3405.

Abstract

Camphorataimide B (CamB) has anticancer activities against several tumors. Here, we aimed to investigate the mechanism(s) by which CamB inhibits metastasis of colorectal cancer (CRC) cells. Low-dose CamB did not affect the cell viability and cell cycle progression of CRC cells, but significantly inhibited the metastatic potentials of CRC cells. Mechanically, CamB reduced the protein and mRNA expression of BMP4, and inhibited Smad and FAK/Src/Akt signaling. CamB also decreased Snail levels by promoting its degradation via proteasome and thereafter reduced Snail-mediated BMP4 transcription. Moreover, CamB considerably inhibited the in vivo metastasis of DLD-1 cells in xenograft mice.

摘要

樟脑酰胺B(CamB)对多种肿瘤具有抗癌活性。在此,我们旨在研究CamB抑制结直肠癌(CRC)细胞转移的机制。低剂量的CamB不影响CRC细胞的细胞活力和细胞周期进程,但显著抑制CRC细胞的转移潜能。从机制上讲,CamB降低了BMP4的蛋白质和mRNA表达,并抑制了Smad和FAK/Src/Akt信号传导。CamB还通过促进其经蛋白酶体降解来降低Snail水平,进而减少Snail介导的BMP4转录。此外,CamB显著抑制了异种移植小鼠中DLD-1细胞的体内转移。

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