| Objective: Prostate cancer(Pca)has become one of the most common malignant tumors and threatening the health.Therefore,it is urgent to explore new strategy to prevent and treat prostate cancer clinically.Chinese traditional medicine in the treatments of prostate related diseases have been reported.The active ingredients of ginger have a variety of pharmacological effects with low side effects in the treatment for many diseases.However,the role of 6-Gingerol and its underlying mechanism in prostate cancer cells has not yet been explored.Methods: Human prostate cancer cell line,PC3,DU145 and LNCa P,were used in this study.The present study aimed to determine the anticancer mechanism of action of6-Gingerol in prostate cancer cells.The MTT was used to evaluate the effect of 6-Gingerol on cell viability in the presence or absence of docetaxel,LPS,the autophagy inhibitor LY294002 or the ferroptosis inhibitor Ferrostatin-1 in prostate cancer cell.The cell adhesion activity was determined in the presence or absence of LPS or Fibronectin with6-Gingerol-treated prostate cancer cells..The colony assay was used to evaluate the effect of 6-Gingerol on the colony formation ability in prostate cancer cells.Wound healing assay and Transwell assay were used to detect the effect of 6-Gingerol on the migration and invasion in LPS-stimulated or LPS-unstimulated PC3 and DU145 cells.The protein expression of LC3 B,Beclin-1,E-cadherin,N-cadherin,Vimentin,ZO-1,GPX4 and NRF2 after 6-Gingerol treatment with/without Ferrostatin-1 in LPS-stimulation or LPS-unstimulation prostate cancer cells were determined by Western Blot.ROS and GSH levels were detected by assay kits.Results: 6-Gingerol(1-500 μM)can inhibit the cell viability and colony formation of prostate cancer cells.6-Gingerol(10 μM)combined with docetaxel(0.05-10 μM)showed a synergistic effect.6-Gingerol(100,500 μM)can reduce the adhesion in LPS-stimulated or LPS-unstimulated prostate cancer cells(PC3,DU145 and LNCa P).The expression of autophagy-related protein LC3 B and Beclin-1 were up-regulated in 6-Gingerol-treated(1-100 μM)prostate cancer cells.Combination of 6-Gingerol with LY294002 increased the cell survival of DU145 cells and decreased the viability of PC3 and LNCa P cells.6-Gingerol(10 μM)inhibited the migration and invasion of LPS-stimulated and LPS-unstimulated PC3 and DU145 cells.6-Gingerol inhibited EMT in prostate cancer cells,including up-regulation of of E-Cadherin and ZO-1 protein expression but down-regulation of N-Cadherin and Vimentin protein expression.6-Gingerol reverses EMT and LC3B-Ⅰexpression in LPS-stimulated DU145 cells.6-Gingerol inhibited GPX4 and NRF2 protein expression in prostate cancer cells.6-Gingerol(100 μM)regulated the expression of ROS and GSH levels in prostate cancer cells.The cell survival rate and GSH levels in the Ferrostatin-1 combined with 6-Gingerol group was higher than that in 6-Gingerol group.But the ROS levels was lower in the Ferrostatin-1 combined with 6-Gingerol group than that in 6-Gingerol group.Conclusion: Our study reported the LPS cause tumor microenvironment and malignant biological behavior in prostate cancer.6-Gingerol inhibited cell viability,migration and invasion in LPS-stimulated and LPS-unstimulated prostate cancer cells.6-Gingerol can regulate EMT-related protein expression levels,prevent migration,invasion and promote autophagy in prostate cancer.6-Gingerol significantly inhibits the growth of prostate cancer by regulating ferroptosis. |
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