研究动态
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Polyphyllin VII 通过 EGFR 通路调节诱导 CTC 失巢抑制肺癌转移。

Polyphyllin VII induces CTC anoikis to inhibit lung cancer metastasis through EGFR pathway regulation.

发表日期:2023
作者: Zujun Que, Bin Luo, Pan Yu, Dan Qi, Wenji Shangguan, Panpan Wang, Jiajun Liu, Yan Li, He Li, Ronghu Ke, Erxi Wu, Jianhui Tian
来源: International Journal of Biological Sciences

摘要:

循环肿瘤细胞(CTC)是从原发肿瘤脱离并进入血流的细胞,在肺癌的转移中发挥着至关重要的作用。不幸的是,目前缺乏专门针对 CTC 和预防肿瘤转移的药物。在这项研究中,我们提供的证据表明,多茶素 VII(一种有效的抗癌化合物)可以通过在 CTC 中诱导一种称为失巢凋亡的过程来有效抑制肺癌的转移。我们观察到,重楼素 VII 在我们新建立的细胞系 CTC-TJH-01 和商业肺癌细胞系 H1975 中具有显着的细胞毒性,并抑制集落形成、迁移和侵袭。此外,我们发现多茶素 VII 诱导失巢凋亡并下调 TrkB 和 EGFR-MEK/ERK 信号通路。此外,TrkB蛋白的激活并不能逆转polyphyllin VII对CTC的抑制作用,而EGFR蛋白的上调则有效地逆转了这种抑制作用。此外,我们的免疫缺陷小鼠模型重现了多茶素 VII 抑制肺转移(这与 EGFR 蛋白的下调有关),并通过诱导失巢凋亡减少了播散到肺部的 CTC 数量。总之,这些结果表明,重楼素 VII 可能是一种有前途的化合物,可通过靶向 CTC 来治疗肺癌转移。© 作者。
Circulating tumor cells (CTCs) are cells that detach from the primary tumor and enter the bloodstream, playing a crucial role in the metastasis of lung cancer. Unfortunately, there is currently a lack of drugs specifically designed to target CTCs and prevent tumor metastasis. In this study, we present evidence that polyphyllin VII, a potent anticancer compound, effectively inhibits the metastasis of lung cancer by inducing a process called anoikis in CTCs. We observed that polyphyllin VII had significant cytotoxicity and inhibited colony formation, migration, and invasion in both our newly established cell line CTC-TJH-01 and a commercial lung cancer cell line H1975. Furthermore, we found that polyphyllin VII induced anoikis and downregulated the TrkB and EGFR-MEK/ERK signaling pathways. Moreover, activation of TrkB protein did not reverse the inhibitory effect of polyphyllin VII on CTCs, while upregulation of EGFR protein effectively reversed it. Furthermore, our immunodeficient mouse models recapitulated that polyphyllin VII inhibited lung metastasis, which was associated with downregulation of the EGFR protein, and reduced the number of CTCs disseminated into the lungs by inducing anoikis. Together, these results suggest that polyphyllin VII may be a promising compound for the treatment of lung cancer metastasis by targeting CTCs.© The author(s).