| Objective: Palmitic acid is a sixteen-carbon long-chain saturated fatty acid that is extracted from the mesocarp of palm fruit.Palmitic acid has a wide range of biological and pharmacological activities.Studies have shown that palmitic acid is associated with insulin resistance,cardiovascular disease,metabolic syndrome,neuropsychiatric disorders,and inflammation.At present,palmitic acid was reported to inhibit the proliferation of breast cancer cells and reduce the activity of myeloma cells,but its effect on human prostate cancer has not been reported.This article was aimed to investigate the effect of palmitic acid in inhibiting prostate cancer and its molecular mechanism,which will provide a theoretical basis for the development of new antitumor lead compound and its application in the clinical treatment of prostate cancer.Method: 1.The effects of Palmitic acid on the proliferation of human prostate cancer cells PC3,DU145,and peripheral blood mononuclearcell PBMC were tested by MTT assay.Soft-agar clone formation assay was used to evaluate the effect of Palmitic acid on the proliferation inhibitory activity and tumorigenicity in PC3 and DU145 cells.2.Annexin V-FITC and PI staining were used to detect the effect of palmitic acid on PC3 and DU145 cell cycle arrest and apoptosis.3.Western blotting assay was used to analyze the expression level of cell cycle regulating factors in prostate cancer cells.4.Western blotting assay was also used to analyze the expression level of the key factors in PI3K/Akt and MAPK pathway in prostate cancer cells.5.Establish a BALB / c nude mouse subcutaneous xenograft model and observe the effect of palmitic acid on tumor growth in vivo.6.The effects of palmitic acid on the migration ability of PC3 and DU145 cells were detected by wound scratches and Transwell cell migration experiments;the effect of palmitic acid on the invasion ability of PC3 and DU145 cells was tested by cell invasion experiments.7.Western blotting assay was used to detect the expression level of PKCζ and E-cadherin,and the phosphorylation of Integrinβ1 with or without palmitic acid treatment.Results: 1.Palmitic acid can inhibit the proliferation of prostate cancer cells PC3 and DU145 in a dose-dependent manner.The results showed that the IC50 values of palmitic acid acting on PC3 and DU145 cells for 48 h were 10.72 μM and 16.83 μM,respectively.The survival rate of PBMC cells treated with high concentration of palmitic acid exceeds 70%,and palmitic acid has low toxicity to human normal cells.Soft agar clone formation experiments proved that palmitic acid can effectively inhibit the tumorigenic ability of PC3 and DU145 in a dose-dependent manner.2.After 48 hours treatment,Palmitic acid arrested the cell cycle at G1 phase in PC3 and DU145 cells,but there was no obvious inducing apoptosis effect was observed in PC3 and DU145 cells.3.The results of Western blotting assays showed that the expression of Cyclin D1 and the phosphorylation level of p Rb were reduced,and the expression of P27 was increased in PC3 and DU145 cells after palmitic acid treatment.4.Western blotting assay also indicated that palmitic acid could inhibit the phosphorylation of PDK-1,Akt,m TOR,and p70S6 K in the PI3K/Akt signaling pathway in PC3 and DU145 cells,and palmitic acid has no effect on the phosphorylation level of ERK in the MAPK signaling pathway.5.Animal experiments show that palmitic acid inhibits tumor growth in vivo in a dose-dependent manner.6.After 24 hours treatment,different concentrations of Palmitic acid(5,10,and 15 μM)inhibited the migration and invasion of PC3 and DU145 cells in a dose-dependent manner.7.Palmitic acid inhibits the invasion and metastasis of PC3 and DU145 cells by inhibiting cell migration and invasion related regulatory factors such as PKCζ,the phosphorylation of Integrinβ1 and up-regulation of E-cadherin.Conclusions: 1.Palmitic acid effectively inhibited the proliferation of prostate cancer cells PC3 and DU145,which was probably through inducing the cell cycle arrest in G1 phase.2.Palmitic acid can inhibit the growth of tumors in the body.3.Palmitic acid could inhibit the migration and invasion of prostate cancer PC3 and DU145 cells.4.Palmitic acid inhibited the proliferation and metastasis of prostate cancer cells via inhibiting PI3K/Akt signaling pathway. |
PDF Full Text Request