Total Flavonoids Of Lichi Seed Diminish Prostate Cancer Progression And Metastasis VIA AKT/mTOR&NF-?B Dual Pathway

Background: Prostate cancer(PCa)is one of the most common malignant tumors in the genitourinary system in the elderly.Its incidence rate is obviously increasing,and PCa is highly prone to metastasis,which causes a variety of complications,leading to death.Therefore,it is particularly urgent to explore the new drugs for the treatment of PCa.In our previous study,we found that total flavonoids of litchi seed(TFLS)can significantly inhibit the growth and metastasis of PCa,but the molecular mechanism is still unclear.In order to investigatethe underlying molecular mechanism of TFLS anti-prostate cancer and its metastases,different experiments on cell cycle regulation,apoptosis,metastasis were designed in vitro.Methods: The effects of TFLS on cell proliferation of PCa cells were explored by MTS assay;Colony formation assay was performed to determine the inhibiting effects of TFLS on PC3 and DU145 cells lines;Flow cytometry was used to detect the effects of TFLS on cell cycle and apoptosis of PC3 and DU145 cells lines;In order to explore the effect of TFLS on the metastasis ofPCa cells,we examined the effect of TFLS on the migration of PC3 and DU145 cells lines by wound healing test,and evaluated the effect of TFLS on the invasion ability of PC3 and DU145 cells lines using Transwell assay;The effects of TFLS on epithelial-mesenchymal transition(EMT)of PCa cells were examined by observing the morphological changes of PCa cells and detecting the expressions of EMT-related protein using Western-Blot;The possible signaling pathways regulated by TFLS were detected by Western-Blot.Results: MTS assay showed that TFLS inhibited the proliferation of PCa cells in vitro;Colony formation assay confirmed that TFLS inhibited the colony forming ability of PCa cells in a dose-dependent manner;Cell cycle and apoptosis experiment found that TFLS had no effect on cell cycle,but it could induce apoptosis of PCa cells;Wound healing test and transwell assay demonstrated that TFLS reduced the migration and invasion ability of PCa cells;The TFLS induced the morphological changes of PCa cells,and up-regulated the expression of E-cadherin and ?-catenin,down-regulated the expression of Vimtenin;We also found that the TFLS have no regulation on p-AMPK ?,Wnt3 a,p-MEK1/2,but it can significantly reduce the expression of p-AKT and its downstream proteins,such as p-NF-kB,p-mTOR and p-I?B ?.Conclusions: TFLS inhibit the growth and metastasis of PCa cells via induction of apoptosis and attenuation of EMT through AKT/mTOR&NF-?B dual signaling.This study provide a theoretical basis for the development and application of TFLS.