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Sci Rep. 2017 Jan 30;7:41616. doi: 10.1038/srep41616.

The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma.

Deng G1,2, Zeng S1,2,3, Ma J2,3, Zhang Y1,2, Qu Y1,2, Han Y1,2, Yin L1,2, Cai C1,2, Guo C1,3, Shen H1,2,3.

Author information

1
Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
2
Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
3
Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Abstract

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.

PMID:
28134289
PMCID:
PMC5278559
DOI:
10.1038/srep41616
[Indexed for MEDLINE]
Free PMC Article

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