Abstract
Background: Colorectal cancer (CRC) is a malignant tumor with high incidence and bad prognosis. Therapies, which are more safety and effective, are urgent needed in clinical. Trypsin is proved to be crucial to cancer proliferation and migration, therefore, it’s possible to control cancers through modulating the activity of trypsin. Fisetin is a flavone with excellent trypsin inhibition that screened from more than 45 compounds derived from traditional Chinese medicine. However, the effects and the mechanisms of fisetin on CRC have not been well investigated. Methods: In this study, we firstly evaluated the expression of trypsin on CRC cells. The effects of fisetin on proliferation and migration of CRC cells were also investigated in vitro. The inhibitory effects on cell cycle and apoptosis were assayed using flow cytometry. The therapeutic activity and toxicity were evaluated in vivo. Results: Fisetin remarkably inhibited CRC cell proliferation and migration, as well as induced cell apoptosis and Go/G1 phase arrest in a dose‐dependent manner. Mechanistic studies revealed these effects were mediated partially through signaling pathways involving cell cycle regulators p21, p27, cyclinD1 and NF kappa B (NF-κB) p65. Administration of fisetin also significantly suppressed the tumor growth in tumor-bearing NOG mice inoculated with human HCT116 cells. Fisetin at the given dosage did not induce significant acute or chronic toxicity in rats.Conclusions: Fisetin can inhibit the growth and migration of CRC by inhibiting the trypsin both in vitro and in vivo. Our results revealed fisetin is a potent therapy for CRC.
Loss of AKR1B10 promotes colorectal cancer cells proliferation and migration via regulating FGF1-dependent pathway
