The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma.
The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma.
复制标题
莲心碱对肝细胞癌中 EMT 通过 Snail 信号传导调节细胞侵袭和奥沙利铂敏感性的抗肿瘤活性
DOI：
10.1038/srep41616
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发表时间：
2017-01-30
影响因子：
4.6
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Deng G;Zeng S;Ma J;Zhang Y;Qu Y;Han Y;Yin L;Cai C;Guo C;Shen H
与上皮间质转化（EMT）相关的肿瘤侵袭和化疗耐药仍然是肝细胞癌（HCC）治疗的主要挑战。甲基莲心碱是莲的天然成分，已被证实具有抗肿瘤作用，但其对肝癌侵袭和化疗敏感性的影响尚需进一步研究。应用细胞增殖、流式细胞术、免疫荧光染色、qRT-PCR、Western blot、荧光分子断层成像等多种检测方法，研究甲基莲心碱对肝癌细胞株HepG 2、Bel-7402以及异种移植动物模型中EMT调控的生存力、凋亡、侵袭力和奥沙利铂（OXA）敏感性的影响。在此，我们报道甲基莲心碱在体外和体内对肝癌细胞增殖没有明显的影响，但显著增强OXA的细胞毒性和凋亡。甲基莲心碱通过上调E-cadherin表达，下调Vimentin、Snail和N-cadherin表达，抑制EMT诱导的肝癌细胞迁移和侵袭能力。TGF-β1可拮抗甲基莲心碱对肝癌细胞迁移和侵袭的抑制作用。Snail过表达或TGF-β1诱导的EMT减弱甲基莲心碱介导的HCC中OXA致敏作用总之，我们的数据表明甲基莲心碱通过抑制HCC细胞中的EMT来增强奥沙利铂的敏感性。甲基莲心碱可作为OXA增敏剂用于HCC化疗。
Tumor invasion and chemotherapy resistance, which are associated with epithelial-mesenchymal transition (EMT), remain as major challenges in hepatocellular carcinoma (HCC) treatment. Neferine, a natural component of Nelumbo nucifera, have been proven the antitumor efficiency in cancer, but the effects of Neferine on HCC invasion and chemosensitivity need to be elucidated. Applying multiple assays of cell proliferation, flow cytometry, immunofluorescence staining, qRT-PCR, Western blot, fluorescence molecular tomography imaging, the influences of Neferine on EMT-regulated viability, apoptosis, invasion, and oxaliplatin (OXA) sensitivity were assessed in HCC cells of HepG2 and Bel-7402, as well as in xenograft animal models in vivo. Here, we reported that Neferine had no obvious effects on HCC cells proliferation, but significantly enhanced cytotoxicity and apoptosis caused by OXA in vitro and in vivo. Through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin, Neferine suppressed EMT-induced migration and invasion abilities of HCC cells. TGF-β1 cancelled the effects of Neferine on the migration and invasion of HCC cells. Snail overexpression or TGF-β1-induced EMT attenuated Neferine-mediated OXA sensitization in HCC. Together, our data suggest that Neferine enhances oxaliplatin sensitivity through an inhibition of EMT in HCC cells. Neferine may be used as an OXA sensitizer in HCC chemotherapy.