The activation of Akt/mTOR pathway by bleomycin in Epithelial-to-mesenchymal transition of human submandibular gland cells: A treatment mechanism of bleomycin for mucoceles of the salivary glands
The activation of Akt/mTOR pathway by bleomycin in Epithelial-to-mesenchymal transition of human submandibular gland cells: A treatment mechanism of bleomycin for mucoceles of the salivary glands
复制标题
博来霉素激活人颌下腺细胞上皮间质转化中的Akt/mTOR通路：博来霉素治疗唾液腺粘液囊肿的机制
DOI：
10.1016/j.biopha.2017.02.098
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发表时间：
2017-06-01
影响因子：
7.5
通讯作者：
Zhao, Ji-Hong
中科院分区：
文献类型：
--
作者：
Cai, Yu;Sun, Rui;Zhao, Ji-Hong
目的：我们先前的研究发现博莱霉素瘤体内注射治疗粘液囊肿是安全有效的。本研究旨在探讨上皮间充质转化(EMT)是否参与了博莱曼对涎腺粘液细胞的治疗作用。材料和方法：分别采用细胞计数试剂盒8法和Annexin V结合法检测人颌下腺细胞(HSG细胞)的增殖和凋亡。用实时荧光定量聚合酶链式反应和免疫印迹分析检测HSG细胞的上皮和间质标志物。结果：大剂量BLM(0.5mU g/mL)明显抑制HSG细胞增殖，诱导细胞凋亡，低剂量BLM(0.05和0.1mU g/mL)作用48h可诱导HSG细胞发生EMT。0.05和0.1mU g/mLBLM可激活Akt/mTOR途径，而不是MAPK途径，并激活转录因子slug和Zeb1。0.05和0.1mU g/mLBLm也能促进HSG细胞的迁移，但抑制细胞的腺泡分化能力。结论：BLM通过Akt/mTOR途径对HSG细胞的治疗作用可能与EMT过程有关。重要的是，结果表明，这一过程的潜在作用，在博莱姆硬化治疗唾液腺粘液囊肿。(C)2017年爱思唯尔·马森公司。版权所有。
Objective: Bleomycin (BLM) has been found safe and highly effective in the treatment of the mucoceles by intralesional injection in our previous study. The present research was designed to investigate whether epithelial-to-mesenchymal transition (EMT) contributes to the therapeutic effects of BLM for mucoceles of the salivary glands.Material and methods: The cell proliferation and apoptosis of human submandibular gland cells (HSG cells) were examined by Cell Counting Kit-8 assay and Annexin V binding assay respectively. Epithelial and mesenchymal markers of HSG cells were measured by real-time quantitative PCR and Western blot analysis. Acinar differentiation and cell migration assays were performed to evaluate HSG cells function.Results: High-dose BLM (>= 0.5 mu g/mL) significantly inhibited the cell proliferation and induced the cell apoptosis, while the treatment with low-dose BLM (0.05 and 0.1 mu g/mL) for 48 h induced EMT in HSG cells. Furthermore, Akt/mTOR pathway, rather than MAPK pathway, was activated through treated with 0.05 and 0.1 mu g/mL BLM, as well as activation of the transcription factor Slug and Zeb 1. The migration of HSG cells was also enhanced through 0.05 and 0.1 mu g/mL BLM, but the ability of acinar differentiation was diminished.Conclusion: Our results indicated that an EMT process was involved in the BLM-induced therapeutic effects on the HSG cells through the Akt/mTOR pathway. Importantly, the results indicated the potential role of this process in the BLM sclerotherapy of mucoceles of the salivary glands. (C) 2017 Elsevier Masson SAS. All rights reserved.