School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2019 Oct;42(4):1451-1458. doi: 10.3892/or.2019.7245. Epub 2019 Jul 23.
Epithelial‑mesenchymal transition (EMT) is closely related to tumor metastasis, and offers insight into novel strategies for cancer treatment. HMQ‑T‑F2 (F2) is a taspine derivative, which has excellent anticancer activity in human cervical cancer. The present study aimed to evaluate the effect of F2 on in vitro migration of HeLa cells. The present data demonstrated that F2 inhibited migration of HeLa cells by negatively regulating the Wnt signaling pathway and reversing EMT. F2 not only mediated Frizzled8, p‑LRP6 and LRP6 expression, but also downregulated the phosphorylation of GSK3β, and concurrently decreased the nucleus protein expression of MMP2, MMP3, MMP7, MMP9, and c‑Myc. In addition, the expression of N‑cadherin, vimentin, Snail and HIF‑1α were downregulated and that of E‑cadherin was upregulated after F2 treatment. F2 was also associated with the downregulation of the PI3K/Akt/mTOR signaling pathways. Notably, F2 induced HeLa cell accumulation at the S phase and cell apoptosis. These results provide evidence that F2 inhibits HeLa cell migration, proliferation and promotes apoptosis. It also reverses EMT, potentially via the PI3K/Akt signaling pathway. Therefore, F2 may be a potential therapeutic reagent against cervical cancer.
上皮-间充质转化（EMT）与肿瘤转移密切相关，为癌症治疗的新策略提供了思路。HMQ-T-F2（F2）是一种紫杉烷衍生物，在人宫颈癌中具有优异的抗癌活性。本研究旨在评估 F2 对 HeLa 细胞体外迁移的影响。本研究数据表明，F2 通过负向调控 Wnt 信号通路和逆转 EMT 抑制 HeLa 细胞迁移。F2 不仅介导 Frizzled8、p-LRP6 和 LRP6 的表达，还下调了 GSK3β 的磷酸化，同时降低了 MMP2、MMP3、MMP7、MMP9 和 c-Myc 的核蛋白表达。此外，F2 处理后 N-钙黏蛋白、波形蛋白、Snail 和 HIF-1α 的表达下调，E-钙黏蛋白的表达上调。F2 还与 PI3K/Akt/mTOR 信号通路的下调有关。值得注意的是，F2 诱导 HeLa 细胞在 S 期积累和细胞凋亡。这些结果表明，F2 抑制 HeLa 细胞迁移、增殖并促进细胞凋亡。它还可能通过 PI3K/Akt 信号通路逆转 EMT。因此，F2 可能是一种治疗宫颈癌的潜在治疗试剂。
