Open Access
ARTICLE
PAR2 Inhibition Enhanced the Sensitivity of Colorectal Cancer Cells to 5-FU and Reduced EMT Signaling
Qiuying Quan*1,
Fengyun Zhong†1,
Xinwei Wang‡, Kai Chen§, Lingchuan Guo*
* Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
† Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
‡ Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, P.R. China
§ Department of Oncology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
Oncology Research 2019, 27(7), 779-788. https://doi.org/10.3727/096504018X15442985680348
Abstract
The aim of this study was to investigate the underlying mechanisms that transforming growth factor-
(TGF- )-mediated epithelial-to-mesenchymal transition (EMT) in tumor cells contributes to 5-FU resistance.
A series of experiments involving cell viability and caspase activity analyses, siRNA transfection, RNA isolation, and quantitative-PCR (qPCR) assay, cell migration analysis, Western blotting analysis of total protein and
membrane protein were performed in this study. Mouse xenograft model was used to determine the effect of
the PAR2 inhibitor in vivo. In this study, we found that protease-activated receptor 2 (PAR2) induction in 5-FU
therapy is correlated with TGF- -mediated EMT and apoptosis resistance. PAR2 and TGF- were both activated in response to 5-FU treatment in vivo and in vitro, and whereas TGF- inhibition sensitized CRC cells
to 5-FU and suppressed cell migration, PAR2 activation eliminated the effect of TGF- inhibition. Conversely,
siRNA-mediated PAR2 depletion or PAR2 inhibition with a specific inhibitor produced a similar phenotype as
TGF- signal inhibition: 5-FU sensitization and cell migration suppression. Moreover, the results of xenograft
experiments indicated that the PAR2 inhibitor can enhance cell killing by 5-FU in vivo and suppress EMT signaling. Our results reveal that the TGF- effects require the coordinating action of PAR2, suggesting that PAR2
inhibition could be a new therapeutic strategy to combat 5-FU resistance in CRC.
Keywords
Cite This Article
APA Style
Quan, Q., Zhong,
.F., Wang,
.X., Chen, K., Guo, L. (2019). PAR2 inhibition enhanced the sensitivity of colorectal cancer cells to 5-FU and reduced EMT signaling. Oncology Research, 27(7), 779-788. https://doi.org/10.3727/096504018X15442985680348
Vancouver Style
Quan Q, Zhong
F, Wang
X, Chen K, Guo L. PAR2 inhibition enhanced the sensitivity of colorectal cancer cells to 5-FU and reduced EMT signaling. Oncol Res. 2019;27(7):779-788 https://doi.org/10.3727/096504018X15442985680348
IEEE Style
Q. Quan,
.F. Zhong,
.X. Wang, K. Chen, and L. Guo "PAR2 Inhibition Enhanced the Sensitivity of Colorectal Cancer Cells to 5-FU and Reduced EMT Signaling," Oncol. Res., vol. 27, no. 7, pp. 779-788. 2019. https://doi.org/10.3727/096504018X15442985680348