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Plumbagin promotes human hepatoma SMMC-7721 cell apoptosis via caspase-3/vimentin signal-mediated EMT

Authors Wei Y, Lv B, Xie J, Zhang Y, Lin Y, Wang S, Zhong J, Chen Y, Peng Y, Ma J

Received 10 February 2019

Accepted for publication 19 June 2019

Published 15 July 2019 Volume 2019:13 Pages 2343—2355

DOI https://doi.org/10.2147/DDDT.S204787

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Cristiana Tanase


Yanfei Wei,1,* Beibei Lv,1,* Jinling Xie,2,* Yuan Zhang,3 Yuning Lin,1 Shengshan Wang,1 Jing Zhong,1 Yongxin Chen,1 Yue Peng,1 Jing Ma1

1Department of Physiology, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, People’s Republic of China; 2Medical Science Experimental Center, Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi 530200, People’s Republic of China; 3Department of State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 710032, People’s Republic of China

*These authors contributed equally to this work

Background/aims: Plumbagin (PL) has been shown to effectively inhibit tumor growth and migration of hepatocellular carcinoma cells in previous studies, but the specific mechanism for this remains unclear. The purpose of this study was to investigate the effects of PL-induced apoptosis in epithelial–mesenchymal transition (EMT) of human hepatocellular carcinoma (HCC) in vivo and in vitro.
Methods: SMMC-7721 cells were cultured, an EMT model was induced in vitro by TGF-β1, cell proliferation was detected by the MTT assay, cell invasion was analyzed by the Transwell invasion assay, and the apoptosis rate was measured by flow cytometry. RT-PCR was used to detect vimentin, E-cadherin, N-cadherin and snail mRNA, and Western blotting was used to detect the vimentin, caspase-3, PARP-1, E-cadherin, N-cadherin and snail protein expression levels. HE staining and TUNEL staining, immunohistochemistry and immunofluorescence were used to detect the expression levels of bax and bcl-2 in hepatocarcinoma xenografts and to evaluate their apoptosis in vivo.
Results: The in vitro results showed that PL inhibited the proliferation of EMT model cells, increased the apoptosis rate of the EMT model, and significantly decreased the vimentin, PARP-1, N-cadherin and snail protein levels, but significantly increased E-cadherin and caspase-3 protein expression. In addition, the in vivo results indicated that PL can affect the expression of bax/bcl-2 apoptotic marker proteins.
Conclusion: PL may induce apoptosis of human hepatocellular carcinoma cells undergoing epithelial–mesenchymal transition by increasing the caspase-3 protein level and cleaving vimentin.

Keywords: plumbagin, hepatocellular carcinoma, epithelial-mesenchymal transition, apoptosis, caspase-3
 

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