Abstract
Pancreatic cancer is an extremely malignant digestive tract tumor. With the increase of chemotherapeutic resistance of pancreatic cancer, clinical treatment is in a dilemma. Hence, it is pivotal to design an effective drug for treating individuals with pancreatic cancer. Fisetin extracted from vegetables, as well as fruits was explored to possess antioxidant, anti-cancer, anti-inflammatory along with anti-microbial properties. Nonetheless, there is limited research focusing on the utility of fisetin as an inhibitor of pancreatic cancer. Similarly, the mechanism through which Fisetin dampens pancreatic cancer remains unknown. This research work systematically evaluated the possible anti-cancer influences of fisetin in pancreatic cancer, as well as explored its responsible molecular mechanism. Our data revealed that fisetin obviously dampens pancreatic cancer progress in vitro along with in vivo dose-dependently. Furthermore, we established that fisetin repressed pancreatic cancer via explicitly targeting PI3K/AKT/mTOR signaling cascade and not the JAK2 cascade. Our data clarified that fisetin is a prospective anti-cancer drug for pancreatic cancer, as well as indicated the distinct molecular target of fisetin.
Highlights
Pancreatic cancer (PC) is a fatal malignancy with a median survival time of six months after diagnosis and a five-year overall survival (OS) of only 5% [1, 2]
Our results suggested that fisetin inhibited proliferation, infiltration along with migration and triggered pancreatic cancer cells apoptosis through targeting the PI3K/protein kinase B (AKT)/mTOR cascade
Immunofluorescence staining exhibited that proliferation of the PANC-1 cells along with Patu-8988 cells remarkably decreased after treatment with 50 μM or 100 μM fisetin (Figures 1E, 1F, 2C, 2D)
Summary
Pancreatic cancer (PC) is a fatal malignancy with a median survival time of six months after diagnosis and a five-year overall survival (OS) of only 5% [1, 2]. It is dominated by pancreatic ductal adenocarcinoma, a most common type accounting for approximately 95% of all PCs [3, 4]. Adjuvant chemotherapy may improve the condition or expand the life of PC patients who are not suitable for curative surgery. It causes severe side effects on patients, such as constipation, loss of appetite, vomiting, nausea, etc.
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