厚朴酚誘導三陰性乳癌細胞凋亡並抑制上皮間質轉化

在三陰性乳癌（triple negative breast cancer, TNBC）中，上皮間質轉化（epithelial-mesenchymal transition, EMT）過程導致增加侵襲能力和對化學治療的抗藥性。厚朴酚（magnolol）是一種在植用物厚朴中發現的生物活性化合物，已報導可以減緩結腸癌細胞的EMT。然而，厚朴酚是否抑制TNBC細胞的EMT仍不清楚。因此，本研究的主要目的是驗證厚朴酚對TNBC細胞的EMT的影響。將TNBC MDA-MB-231和4T1細胞用不同濃度的厚朴酚處理48小時。使用流式細胞儀和西方墨點評估厚朴酚對細胞週期分佈和EMT相關蛋白的影響。結果顯示，厚朴酚明顯誘導TNBC細胞凋亡，降低N-cadherin、zinc finger E-box binding homeobox 1（ZEB1）、ZEB2、Snail、Slug和Twist的蛋白水平，同時增加E-cadherin的表現。從Kaplan-Meier plotter（KMplot）獲得的信息顯示，Snail水平較低的TNBC患者比Snail水平較高的患者有更有利的預後。誘導細胞凋亡和減少EMT相關蛋白可能參與厚朴酚介導的抗TNBC效應。

關鍵字

三陰性乳癌；厚朴酚；細胞凋亡；上皮間質轉化

並列摘要

Background/Aim: In triple negative breast cancer (TNBC), the process of epithelial to mesenchymal transition (EMT) contributes to increased invasion ability and resistance to chemotherapy. Magnolol, a bioactive compound found in the medicinal plant Magnolia officinalis, has been reported to attenuate epithelial to mesenchymal transition (EMT) of colon cancer cells. However, it is unclear whether magnolol inhibits EMT of TNBC cells. Therefore, the main goal of the present study was to verify the effect of magnolol on EMT in TNBC cells. Materials and Methods: Both TNBC MDA-MB-231 and 4T1 cells were treated with different concentration of magnolol for 48 h. Effects of magnolol on cell cycle distribution and EMT-related proteins were evaluated by using flow cytometry and Western blotting assay. Results: The results showed that magnolol significantly induced apoptosis and reduced protein levels of N-cadherin, zinc finger E-box binding homeobox 1 (ZEB1), ZEB2, Snail, Slug, and Twist, while increasing expression of E-cadherin. Information obtained from the Kaplan-Meier plotter (KM plot) indicated that TNBC patients with low levels of Snail had a more favorable prognosis compared to those with high levels. Conclusion: the induction of apoptosis and reduction of EMT-related proteins may be involved in the magnolol-mediated anti-TNBC effects.

並列關鍵字

TNBC ； magnolol ； apoptosis ； EMT

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