?-catenin inhibitors suppress cells proliferation and promote cells apoptosis in PC9 lung cancer stem cells.

ABSTRACT: This study aimed to investigate the effect of ?-catenin inhibitors on cells proliferation and apoptosis in lung cancer stem cells (LCSCs). Drug-resistance PC9 cells were induced by escalation of cisplatin repeated treatment, and then PC9 LCSCs were constructed by Sphere Formation methods. Membrane expression of OCT4, SOX2, CD44, CD133 and ?-Catenin were detected by Immunofluorescent staining, and mRNA of CSCs marker genes and Wnt/?-Catenin target genes were determined by qPCR assay. PC9 LCSCs were nurtured for 5 days (Day 5) and then ?-catenin inhibitor pyrvinium pamoate (PP) with IC50 concentration (0.221 µM) and ICG-100 with IC50 concentration (2.620 µM) were added and cultured for another 2 days (Day 7), respectively. CCK8 and AV/PI assays were performed to detect cells proliferation and apoptosis. We successfully constructed PC9 LCSCs and observed that OCT4, SOX2, CD44, CD133 and ?-Catenin expressed on all cells, and stem-cell marker genes as well as Wnt/?-Catenin signaling pathway genes mRNA were all elevated in PC9 LCSCs compared to PC9 parent cells. Cells proliferation by CCK8 assay was decreased while apoptosis rate by AV/PI assay was increased in PP treatment group compared with control, C-Caspase 3 and Bcl-2 protein expression also supported the apoptosis results. Most of the stem-cell marker genes and Wnt/?-Catenin signaling pathway genes mRNAs were decreased accordingly. ICG-001 also inhibited cells proliferation while induced cells apoptosis in PC9 LCSCs. In conclusion, ?-Catenin inhibitors suppressed the proliferation and promoted the apoptosis of LCSCs, which shed light on a new potential target for lung cancer treatment.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC6966044 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature