Itraconazole inhibits invasion and migration of pancreatic cancer cells by suppressing TGF-β/SMAD2/3 signaling

Oncology Reports
Ke ChenWei Yang

Abstract

Pancreatic cancer is the fourth leading cause of cancer-associated mortality worldwide, with an overall 5-year survival rate <8%. We studied the therapeutic effect of itraconazole (ITZ), a commonly used broad-spectrum anti-fungal agent, in the treatment of pancreatic cancer, and to reveal the underlying anticancer mechanisms. Effects of ITZ on cell proliferation, apoptosis, invasion and migration were observed by MTT assays and colony formation assays, flow cytometry, wound scratch assays and transwell assays, respectively. Western blotting and immunofluorescence were performed to investigate the effect of ITZ on the epithelial to mesenchymal transition (EMT) of pancreatic cancer cells. Recombinant transforming growth factor-β (TGF-β) and TGF-β neutralizing antibody were used to study the effect of ITZ on the TGF-β/SMAD2/3 signaling. Transgenic engineered mice which harboring the spontaneous pancreatic cancer was applied to investigate the therapeutic role of ITZ in vivo. We report that ITZ inhibited the viability and induced apoptosis of pancreatic cancer cells. Furthermore, ITZ suppressed the invasion and migration of pancreatic cancer cells. We found that ITZ treatment was efficient in suppressing EMT and that the effect of ...Continue Reading

Citations

Apr 3, 2021·Molecular Biology Reports·Shruti GuptaKiran Kumar Tejavath
Apr 4, 2021·Pharmaceuticals·Rita RebeloCristina P R Xavier

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