| Objective: Prostate cancer is the second most common malignant tumor in men worldwide,and it is a cancer formed in prostate tissue.There are many risk factors for prostate cancer,including fixed factors that cannot be changed,such as age,race/ethnicity,history of local or family disease,and external factors that can be changed,such as endogenous hormone disorders,chronic inflammation,urinary tract infections,unhealthy lifestyle and obesity.The external factors that can be changed,such as infection,have received the unanimous attention of scholars.At present,it is generally believed that various chronic inflammations caused by infections and non-infection can promote tumorigenesis and tumor development via inducing various genetic and epigenetic changes.Infection is one of the main drivers of inflammation-induced tumorigenesis.The relationship between infection and inflammation and prostate cancer is inseparable.Repeated infection of Gram-negative bacilli is an important cause of chronic prostatitis.Moreover,there is a wealth of evidence that infection promotes the development and progression of prostate cancer.Contrary to risk factors,research shows that sun exposure reduces the risk of prostate cancer and is therefore a protective factor for prostate cancer.It is thought that the reason is that sunlight can increase the content of calcitriol in the human body,but its specific protective mechanism is unknown.In view of this,our study has explored the protective effects of calcitriol(Calcitriol)on the main components of Gram-negative bacilli—lipopolysaccharide stimulated prostate cancer cells in cell proliferation,migration and invasion.Methods: PC3 and DU145 cells were treated with or without calcitriol and then stimulated with LPS(2.0 ?g / m L)or not.The cells were therefore divided into 4 groups.Flow cytometry was used to detect the effects of the above treatments on the cell cycle.Scratch experiments,Transwell migration and invasion experiments were used to detect the malignancy of each group of cells.RT-PCR was used to detect the expression of related m RNAs.ELISA kits were used to determine the culture supernatant IL-6 and IL-8 levels;NF-?B / p65 signal,IL-6 / STAT3 signal and VDR signal pathway-related protein expression in each group of cells were detected by Western blotting;Co-immunoprecipitation was used to detect the interaction between VDR and STAT3.Results: Calcitriol treatment inhibited the increase of the proportion of PC-3 cells in S phase induced by LPS,and reduced the levels of Cyclin D1 protein and PCNA protein in the nucleus of PC-3 cells,but it was not observed in DU145 cells.In addition,Transwell and scratch experiments showed that calcitriol can inhibit the migration and invasion of PC3 and DU145 cells induced by LPS.Further studies have observed that calcitriol inhibits the activity of NF-?B and promotes the synthesis and secretion of IL-6 and IL-8by promoting the protein-protein interaction between VDR and NF-?B P65.And in PC3 and DU145 cells treated with LPS,calcitriol up-regulated the expression of VDR and promoted the physical binding between VDR and p-STAT3,thereby preventing nuclear translocation of p-STAT3.Conclusion: This study investigated the effect of calcitriol on the malignant phenotype of prostate cancer cells stimulated by LPS.Our results show that calcitriol can inhibit the proliferation,migration and invasion of prostate cancer cells induced by LPS.In addition,calcitriol indirectly inhibits STAT3 by promoting the interaction between VDR and NF-?B p65,inhibiting LPS-mediated activation of NF-?B signaling and subsequent expression and secretion of IL-6 and IL-8.Importantly,calcitriol directly inhibitednuclear transcription of p STAT3 in prostate cancer cells induced by LPS by enhancing the interaction between VDR and p STAT3.In summary,this study found that calcitriol inhibits LPS-mediated proliferation,migration,and invasion of prostate cancer cells by directly and indirectly blocking STAT3 signaling. |
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