Acacetin inhibits invasion, migration and TGF-β1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway.
Acacetin inhibits invasion, migration and TGF-β1-induced EMT of gastric cancer cells through the PI3K/Akt/Snail pathway.
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DOI：
10.1186/s12906-021-03494-w
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发表时间：
2022-01-09
影响因子：
3.9
通讯作者：
Zhao A
中科院分区：
文献类型：
--
作者：
Zhang G;Li Z;Dong J;Zhou W;Zhang Z;Que Z;Zhu X;Xu Y;Cao N;Zhao A
上皮细胞向间质细胞转化（EMT）是一种重要的细胞现象，参与肿瘤的转移和进展。EMT是胃癌术后复发和转移的主要原因。金合欢素具有多种生物活性。然而，金合欢素对胃癌EMT的抑制作用尚不清楚。本研究旨在探讨金合欢素在体内外对胃癌EMT影响的可能机制。体外实验中，用金合欢素处理MKN 45和MGC803细胞，CCK-8法检测细胞活力，Transwell法和创伤愈合法检测细胞迁移和侵袭能力，Western blot和免疫荧光染色法检测蛋白表达。在体内，使用MKN 45 GC细胞的腹膜转移模型来研究金合欢素的作用。金合欢素通过调节EMT相关蛋白的表达抑制人胃癌细胞MKN 45和MGC 803的增殖、侵袭和迁移。在TGF-β 1诱导的EMT模型中，金合欢素逆转了上皮细胞向间充质细胞的形态学改变，并通过调节EMT限制侵袭和迁移。此外，金合欢素抑制PI3K/Akt信号通路的激活，并降低TGF-β 1处理的GC细胞的磷酸化水平。体内实验表明金合欢素能延缓胃癌裸鼠腹腔转移。通过改变EMT相关蛋白的表达抑制肝转移。我们的研究表明金合欢素能抑制胃癌的侵袭、转移和TGF-β 1诱导的EMT，其机制可能与抑制PI3K/Akt/Snail信号通路有关。因此，金合欢素是一种潜在的治疗复发转移胃癌的药物。在线版本包含补充材料，可通过10.1186/s12906 - 021 - 03494-w获得。
Epithelial-to-mesenchymal transition (EMT) is a pivotal cellular phenomenon involved in tumour metastasis and progression. In gastric cancer (GC), EMT is the main reason for recurrence and metastasis in postoperative patients. Acacetin exhibits various biological activities. However, the inhibitory effect of acacetin on EMT in GC is still unknown. Herein, we explored the possible mechanism of acacetin on EMT in GC in vitro and in vivo. In vitro, MKN45 and MGC803 cells were treated with acacetin, after which cell viability was detected by CCK-8 assays, cell migration and invasion were detected by using Transwell and wound healing assays, and protein expression was analysed by western blots and immunofluorescence staining. In vivo, a peritoneal metastasis model of MKN45 GC cells was used to investigate the effects of acacetin. Acacetin inhibited the proliferation, invasion and migration of MKN45 and MGC803 human GC cells by regulating the expression of EMT-related proteins. In TGF-β1-induced EMT models, acacetin reversed the morphological changes from epithelial to mesenchymal cells, and invasion and migration were limited by regulating EMT. In addition, acacetin suppressed the activation of PI3K/Akt signalling and decreased the phosphorylation levels of TGF-β1-treated GC cells. The in vivo experiments demonstrated that acacetin delayed the development of peritoneal metastasis of GC in nude mice. Liver metastasis was restricted by altering the expression of EMT-related proteins. Our study showed that the invasion, metastasis and TGF-β1-induced EMT of GC are inhibited by acacetin, and the mechanism may involve the suppression of the PI3K/Akt/Snail signalling pathway. Therefore, acacetin is a potential therapeutic reagent for the treatment of GC patients with recurrence and metastasis. The online version contains supplementary material available at 10.1186/s12906-021-03494-w.
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