Beclin1 inhibits proliferation, migration and invasion in tongue squamous cell carcinoma cell lines
Beclin1 inhibits proliferation, migration and invasion in tongue squamous cell carcinoma cell lines
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Beclin1抑制舌鳞状细胞癌细胞系的增殖、迁移和侵袭
DOI：
10.1016/j.oraloncology.2014.06.020
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发表时间：
2014-10-01
期刊：
影响因子：
4.8
通讯作者：
Hou, Jinsong
中科院分区：
文献类型：
--
作者：
Weng, Junquan;Wang, Cheng;Hou, Jinsong
目的：自噬在肿瘤发生发展中的作用仍存在争议。在我们以前的研究中，我们证实了自噬活性的降低促进舌鳞状细胞癌（TSCC）的恶性进展。然而，自噬相关蛋白Beclin 1在TSCC中的作用尚未得到充分的证实。本研究旨在阐明beclin 1在TSCC发生发展中的作用，并探讨其可能的机制。材料与方法：采用慢病毒BECN 1和sh-BECN 1转染TSCC细胞株SCC 9和SCC 15，建立稳定的TSCC细胞系。然后用qPCR和western blot检测Beclin 1的表达。Western blot和ELISA检测自噬相关蛋白和肿瘤转移相关蛋白的表达。MTT法检测细胞增殖活性，transwell法检测细胞迁移和侵袭能力。结果：BECN 1和sh-BECN 1病毒转染后，Beclin 1的mRNA和蛋白表达均显著增加或降低。同时，我们还观察到Beclin 1可以增强LC 3-II、ATG 4和ATG 5的表达水平。Beclin 1的过表达抑制了TSCC细胞的增殖、迁移和侵袭，而Beclin 1的敲低则促进了TSCC细胞的增殖、迁移和侵袭。此外，我们证明，血管内皮生长因子（VEGF），基质金属蛋白酶-2和-9参与Beclin 1介导的迁移和侵袭抑制。结论：自噬调控基因Beclin 1可能与TSCC细胞的恶性表型有关，Beclin 1可能是口腔癌基因治疗的潜在靶点。(C)2014爱思唯尔有限公司版权所有。
Objectives: The role of autophagy is still a controversy in cancer development. In our previous study, we confirmed that decrease of autophagy activity promotes malignant progression of tongue squamous cell carcinoma (TSCC). However, the role of autophagy-related protein, Beclin1, has not well been documented in TSCC. In this study, we aim to elucidate the role of beclin1 in TSCC progression and investigate its potential mechanisms.Materials and methods: TSCC cell lines, SCC9 and SCC15 were used to generate the stable cells with transfection lentivirus BECN1 and sh-BECN1. Then, Beclin1 expression was detected with qPCR and western blot. Moreover, the expressions of autophagy-related proteins and tumor metastasis associated proteins were examined by western blot and ELISA. For functional analysis, MTT assay were performed to evaluate the proliferation activity and transwell assay was used to assess the migration and invasion ability. Finally, TSCC xenograft models were established to confirm the effect of Beclin1 on TSCC in vivo.Results: The results showed that BECN1 and sh-BECN1 virus transfection significantly increased or decreased the mRNA and protein expression of Beclin1 in the transfected TSCC cells. Meanwhile, we also observed that Beclin1 could enhance the expression levels of LC3-II, ATG4 and ATG5. Then, we revealed that overexpression of Beclin1 inhibited proliferation, migration and invasion while knockdown of Beclin1 promoted proliferation, migration and invasion in TSCC cells. Furthermore, we demonstrated that vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 were involved in Beclin1-mediated inhibition of migration and invasion. More importantly, our data also confirmed that Beclin1 inhibited TSCC xenograft growth in vivo.Conclusion: Taken together, the results indicate that autophagy regulating gene, Beclin1, may contribute to the malignant phenotypes of TSCC cells and can be a potential target for oral cancer gene therapy. (C) 2014 Elsevier Ltd. All rights reserved.