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Exp Mol Pathol. 2019 Apr;107:23-31. doi: 10.1016/j.yexmp.2019.01.008. Epub 2019 Jan 23.

Triptolide inhibits the growth and migration of colon carcinoma cells by down-regulation of miR-191.

Author information

1
Department of Anorectal Surgery, Jining No.1 People's Hospital, Jining 272011, China; Affiliated Jining No.1 People's Hospital of Jining Medical University, Jining Medical University, Jining 272067, China.
2
Department of Anorectal Surgery, Jining No.1 People's Hospital, Jining 272011, China. Electronic address: lijinliang94@sina.com.

Abstract

BACKGROUND:

Triptolide (TPL) is the active component of Tripterygium wifordii Hook F, which has been reported to exert anti-tumor efficacies. Herein, we aimed to examine the efficacy of TPL in colorectal cancer (CRC) cells and to reveal its underlying mechanisms.

METHODS:

Human CRC cell lines HT-29 and SW480 were treated by TPL for 24 h in the presence or absence of epithelial-to-mesenchymal transition (EMT) inducer TGF-β1. The expression of miR-191 in cell was overexpressed by miRNA transfection. Thereafter, cell viability, migration, apoptosis, EMT-related protein expressions, and the activation of NF-κB and Wnt/β-catenin pathways were respectively assessed. Moreover, a mouse model of CRC was established and the effects of TPL on the growth of primary tumors were tested.

RESULTS:

TPL (50 and 100 nM) significantly reduced cell viability and migration, but increased apoptotic cell rate. TPL up-regulated Bax, increased the cleavage of caspase-3 and -9, and neutralized TGF-β1-induced alterations of EMT indicators, including E-cadherin, N-cadherin, Vimentin, and Snail. At the meantime, TPL treatment down-regulated miR-191 expression, and the effect of TPL on miR-191 expression was mediated by EZH2. More interestingly, anti-CRC properties and the inhibitory effects of TPL on NF-κB and Wnt/β-catenin pathways were reversed by miR-191 up-regulation. In vivo data showed that, TPL treatment decreased the growth of primary tumor xenografts and the expression of miR-191.

CONCLUSION:

TPL is effective in killing CRC cells and suppressing the migratory capacity. TPL exerts anti-CRC properties possibly via down-regulating miR-191, and blocking the activation of NF-κB and Wnt/β-catenin pathways.

KEYWORDS:

Colorectal cancer (CRC); HT-29 cell; NF-κB and Wnt/β-catenin pathways; SW480 cell; Triptolide (TPL); miR-191

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