PAR2 inhibition enhanced the sensitivity of colorectal cancer cells to 5-FU and reduced EMT signaling.

In this study, we found that protease-activated receptor-2 (PAR2) induction in 5-Fu therapy is correlated with TGF-β-mediated EMT and apoptosis resistance. PAR2 and TGF-β were both activated in response to 5-Fu treatment in vivo and in vitro, and whereas TGF-β inhibition sensitized CRC cells to 5-Fu and suppressed cell migration, PAR2 activation eliminated the effect TGF-β inhibition. Conversely, siRNA-mediated PAR2 depletion or PAR2 inhibition with a specific inhibitor produced a similar phenotype as TGF-β 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 the TGF-β effects require the coordinating action of PAR2, suggesting that PAR2 inhibition could a new therapeutic strategy to combat 5-Fu resistance in CRC. PMID: 30841957 [PubMed - as supplied by publisher]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research