Mechanism Of Prostate Cancer Progression Induced By Antimony Through Androgen Like Effects

Objective: To explore whether antimony mimics the effects of androgens,and explore its mechanism of action.Methods: First,the optimal concentration of antimony-promoted LNCaP cell proliferation was screened,then LNCaP cells were treated with antimony and androgens respectively under the condition of androgen,and then the antimony was detected by CCK-8 and Transwell.Cell proliferation and invasion.The antimony and androgen antagonist Casodex was treated with LNCaP cells at the same time to observe whether the effect of the above-mentioned proliferation and invasion was decreased or disappeared.It was obvious that the antimony had androgen effects.LNCaP cells were treated with antimony,RT-q PCR and Western Blot were used to detect the expression of AR protein and AR m RNA in LNCaP cells after antimony treatment.The expression of PSA and NKX3.1 m RNA was detected by RT-q PCR method after antimony treatment(P<0.05).The effect of low dose antimony exposure on the expression of AR phosphorylation at different concentrations was investigated by Western Blot.The mechanism of antimony androgen in the antimony was investigated.Results: In the absence of androgen conditions,LNCaP cells almost no proliferation.Low dose of antimony exposure can promote the proliferation of LNCaP cells and promote the proliferation effect with antimony exposure at 0.5u M concentration,which is similar to that of androgen(P<0.05),and its proliferative effect can be antagonized by androgen antagonists.The results showed that antimony exposure and androgen could both enhance the invasive ability of LNCaP cells(P<0.05).The results showed that antimony exposure and androgen also could enhance the invasive ability of LNCaP cells(P<0.05).The results of Western Blot and RT-q PCR showed that antimony exposure had no significant effect on the expression of AR protein and m RNA level.RT-q PCR results showed that low dose of antimony exposure could promote the expression of downstream m RNA and protein of PSA and NKX3.1,and its effects can be antagonized by androgen antagonists,indicating that antimony exposure,although the expression of AR protein and m RNA levels had no significant effect,but can improve the transcription activity of AR.Western Blot results also show in a certain range,with the antimony concentration increased AR phosphorylation level also increased,which shows that antimony can be modified by phosphorylation to achieve the effect of androgen.Conclusion: Low-dose antimony exposure mimics the effects of androgen,which is through the phosphorylation of AR to increase the role of AR transformation activity,and thus promote the occurrence and development of prostate cancer.