Abstract
Drug resistance is a major impediment to successful chemotherapy in pancreatic cancer(PC) patients. We investigated the effect of Wnt/β-catenin signaling inhibition by wnt-c59 on chemoresistance in a trichostatin A-resistant Panc-1 cell line (Panc-1/TSA). Panc-1/TSA cells were treated with the Wnt/β‑catenin signaling inhibitor wnt-c59 (10µmol · l-1) and/or trichostatin A (TSA; 10µmol · l-1) for 24h. CCK-8 assay was utilized to analyze the interactive effect of TSA and wnt-c59 on induction of apoptosis of the Panc-1/TSA cells. Cell apoptosis was measured by flow cytometry. Real-time PCR and western blotting were used to assess Wnt/β-catenin signaling, epithelial-mesenchymal transition(EMT) and multidrug resistance (MDR). Real-time cell analysis(RTCA) was used to detect the cell migration ability. After wnt-c59 treatment for 24h, relative genes and transcriptional targets of Wnt/β-catenin signaling were downregulated (P<0.05). CCK-8 assay indicated that the combination of TSA and wnt-c59 had a synergistic effect on induction of Panc-1/TSA cell apoptosis. As detected by FACS, cell apoptosis rates increased significantly (P<0.05). The results of RTCA showed that the cell indices of the control group, wnt-c59 group, TSA group and TSA+wnt-c59 combination group were 1.2842±0.0257, 1.2155±0.0282, 1.2533±0.0194 and 0.8541±0.0250, respectively. In accordance, MMP-9 protein in the wnt-c59 treatment groups was decreased compared to the non-wnt-c59 treatment groups. Meanwhile, E-cadherin protein was upregulated and vimentin protein was downregulated, both of which are characteristic markers of EMT. Chemoresistant gene MDR1 and P-glycoprotein (P-gp) in the wnt-c59 treatment groups had a reduced expression compared to the non-wnt-c59 treatment groups. This study revealed that TSA sensitivity, migration ability, and the EMT phenotype in Panc-1/TSA cells were reversed following Wnt/β-catenin signaling inhibition.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
