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AIM Our present study aimed to test the anti-cancer effect of natural product ZX-1201 on pancreatic cancer cell PANC-1.METHODS After incubation with different concentrations of drug or vehicle, PANC-1 cell viability was measured by MTS assay, and Scratch assay and Transwell assay were utilized to detect PANC-1 cell migration.Meanwhile, morphological changes were recorded by light microscope.Real-time PCR, immunofluorescence and Western blot were used to examine change of aquaporin-1 (AQP1) and TGF-β1 related EMT pathways.In addition, we performed AQP1 and TGF-β1 RNAi and over-expression experiments to elucidate their role in anti migratiou effect of ZX-1201.RESULTS We found ZX-1201 showed significant inhibitory effect on cell migration in a dose-dependent manner, however, slight cell viability suppression was observed.Next, we demonstrated ZX-1201 could prevent PANC-1 cell from epithelial-mesenehymal transition (EMT), by reducing mesenehymal phenotype, decrease AQP1 and TGF-β1 expression, and dramatically down-regulating EMT markers and signaling pathway.Eventually, we verified that ZX-1201 reversed EMT by targeting AQP1 and TGF-β1, because either AQP1 or TGF-β1 over-expression abolished the inhibitory effect of ZX-1201 on PANC-1.CONCLUSION ZX-1201 significantly inhibits pancreatic cancer cell PANC-1 EMT process through an AQP1 and TGF-β1 targeting manner.