Apoptosis and epithelial-to-mesenchymal transition (EMT) are closely associated with tumor survival and metastasis. These are the basic events in tumor occurrence and progression. STK214947 is an indole alkaloid with a skeleton that is similar to that of indirubin. Indole alkaloids have attracted considerable attention because of their antitumor activity. However, the relationship between STK214947 and these basic events remains unknown. In this study, the effects of STK214947 on inducing apoptosis and reversing the EMT process in tumor cells were confirmed. Mild concentrations of STK214947 inhibited tumor cell migration by reversing EMT and significantly regulated the expression of EMT-related proteins, including Notch3, E-cadherin, N-cadherin and vimentin. In addition, STK214947 in high concentration could induce apoptosis by down-regulating Notch3, p-Akt/Akt, and NF-κB, and upregulating Caspase 3. These findings support the further development of STK214947 as a potential antitumor small molecule that targets Notch3 and Akt signal transduction in cancer.

中文翻译：

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STK214947 是一种新型吲哚生物碱，通过阻断 Notch3 和 Akt 信号来抑制 HeLa 和 SK-HEP-1 细胞的存活和 EMT 过程。

细胞凋亡和上皮间质转化（EMT）与肿瘤的生存和转移密切相关。这些是肿瘤发生和进展的基本事件。STK214947 是一种吲哚生物碱，其骨架与靛玉红相似。吲哚生物碱因其抗肿瘤活性而引起了广泛关注。然而，STK214947与这些基本事件之间的关系仍然未知。本研究证实了STK214947在肿瘤细胞中诱导细胞凋亡和逆转EMT过程的作用。温和浓度的 STK214947 通过逆转 EMT 抑制肿瘤细胞迁移，并显着调节 EMT 相关蛋白的表达，包括 Notch3、E-钙粘蛋白、N-钙粘蛋白和波形蛋白。此外，高浓度的STK214947可以通过下调Notch3、p-Akt/Akt和NF-κB以及上调Caspase 3来诱导细胞凋亡。这些发现支持STK214947作为靶向Notch3和的潜在抗肿瘤小分子的进一步开发。癌症中的 Akt 信号转导。