Brusatol inhibits laryngeal cancer cell proliferation and metastasis via abrogating JAK2/STAT3 signaling mediated epithelial-mesenchymal transition,Life Sciences

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Brusatol inhibits laryngeal cancer cell proliferation and metastasis via abrogating JAK2/STAT3 signaling mediated epithelial-mesenchymal transition
Life Sciences ( IF 5.2 ) Pub Date : 2021-08-25 , DOI: 10.1016/j.lfs.2021.119907
Jiangtao Zhou ₁ , Jing Hou ₁ , Jun Wang ₁ , Jiajing Wang ₁ , Jianping Gao ₁ , Yun'e Bai ₁

Affiliation

This study aimed at investigating the role of Brusatol (BR) on human laryngeal squamous carcinoma cell (Hep-2) to study its underlying mechanism through and approaches. In the present research, we employed various cell-based assays, such as cell proliferation, apoptosis, cell cycle assessment, migration and invasion assays were used to examine the anti-tumor effect of BR on Hep-2 cells. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to study the underlying molecular mechanisms. To validate our findings we used a subcutaneous tumor-bearing model of Balb/c mice with Hep-2 cells of laryngeal carcinoma (LC) to study the inhibitory effect of BR on Hep-2 cells . The results indicated that BR markedly inhibited the viability, migration and invasion capacity of Hep-2 cells, with no significant toxic effect on normal Human bronchial epithelial cell line (BEAS-2B). Also, BR induced cellular apoptosis by blocking the cells in S phase to suppress cell proliferation. Immunohistochemistry results revealed that BR inhibited the protein expression levels of epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, western blotting results exhibited that BR could suppress the protein expression of both JAK2/STAT3 and their phosphorylation levels. Our experiments further validated the anti-tumor effect of BR on Hep-2 cells , where BR suppressed the growth of xenograft laryngeal tumor without apparent toxicity. The present study highlights the anti-LC effect of BR by possibly abrogating JAK2/STAT3 signaling mediated EMT process. BR may be a promising therapeutic candidate for the treatment of LC.

中文翻译：

Brusatol 通过消除 JAK2/STAT3 信号介导的上皮间质转化来抑制喉癌细胞增殖和转移

本研究旨在探讨布鲁萨醇（BR）对人喉鳞状细胞癌细胞（Hep-2）的作用，并探讨其潜在机制和途径。在本研究中，我们采用了各种基于细胞的实验，如细胞增殖、凋亡、细胞周期评估、迁移和侵袭实验来检测BR对Hep-2细胞的抗肿瘤作用。通过免疫组织化学 (IHC)、qRT-PCR 和蛋白质印迹来研究潜在的分子机制。为了验证我们的发现，我们使用具有喉癌（LC）Hep-2细胞的Balb/c小鼠皮下荷瘤模型来研究BR对Hep-2细胞的抑制作用。结果表明，BR显着抑制Hep-2细胞的活力、迁移和侵袭能力，对正常人支气管上皮细胞系(BEAS-2B)无明显毒性作用。此外，BR通过阻断S期细胞来抑制细胞增殖，从而诱导细胞凋亡。免疫组织化学结果显示，BR 抑制上皮间质转化 (EMT) 相关标志物的蛋白表达水平。从机制上讲，蛋白质印迹结果表明 BR 可以抑制 JAK2/STAT3 的蛋白表达及其磷酸化水平。我们的实验进一步验证了BR对Hep-2细胞的抗肿瘤作用，其中BR抑制异种喉肿瘤的生长，且无明显毒性。本研究强调了 BR 的抗 LC 作用，可能是通过消除 JAK2/STAT3 信号介导的 EMT 过程。 BR 可能是治疗 LC 的有前途的候选药物。

更新日期：2021-08-25

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