The Effects of Juglone on Cell Proliferation and Insulin-Like Growth Factor I Receptor/Phosphoinositide 3-Kinase/p85 (IGF-IR/PI3K/p85) Signaling Pathway in Pancreatic Cancer.

Objective: Pancreatic adenocarcinoma is a highly aggressive cancer with a poor prognosis, a high potential for invasion and metastasis, and resistance to therapy. We have previously demonstrated the cytotoxic, apoptotic, and antimetastatic effects of juglone. The insulin-like growth factor I receptor/phosphoinositide 3-kinase (IGF-IR/PI3K) signaling pathway plays an important role in tumor growth, metastasis, and therapeutic resistance in pancreatic cancer. In this study, we aimed to investigate the effect of juglone on cell proliferation in pancreatic cancer and to determine whether its potential effects occur via the IGF-IR/PI3K/p85 signaling pathway. Materials and Methods: The PANC-1 pancreatic cancer cell line was cultured and treated with juglone at concentrations of 5, 10, 15, and 20 µM for 24 hours. The expressions levels of IGF-IR and proliferating cell nuclear antigen (PCNA), an indicator of cell proliferation, as well as p85/PIK3R1 gene transcription, a major downstream molecule of the IGF-IR/PI3K pathway, were evaluated by immunofluorescence analysis and quantitative polymerase chain reaction (qPCR), respectively. Results: Juglone significantly downregulated IGF-IR and PCNA expressions, as well as p85/PIK3R1 transcription in PANC-1 pancreatic cancer cells. These findings suggest that juglone exhibits a potent antiproliferative effect and has the potential to suppress various processes involving the IGF-IR/PI3K/p85 signaling pathway, including tumor growth, metastasis, therapeutic resistance, stemness, and the epithelial-mesenchymal transition (EMT) phenotype of cancer cells. Conclusion: Juglone exerts negative regulatory effects on pancreatic cancer, some of which are likely mediated through the IGF-IR/PI3K/p85 signaling pathway. Therefore, juglone may serve as a potential therapeutic option for the treatment and prevention of the progression of this devastating cancer.