HCI2509 And JQ1,Effect Prostate Cancer Cell Line In Growth And Proliferation

Objective: Herein, we investigate the lysine demethylase 1(LSD1) inhibitor, HCI2509 and combined with JQ1, functions downstream of AR, or respectively treat the Hormone-sensitive prostate cancer cells(LNCa P), and castration resistant cancer cells(DU145).Furthermore, we try to unravel the potential mechanism of compounds on the suppression of proliferation and the induction of apoptosisMethods: Cultured human Hormone-sensitive prostate cancer cells(LNCa P), and castration resistant cancer cells(DU145) treated with the inhibitor of LSD1,HCI2509,and the inhibitor of BRD4,JQ1( separately or in combination).The cell proliferation inhibition rates of human prostate cancer cell were detected by MTT. Cell apoptosis and cell cycle arrest was observed by flow cytometry. We analyze the result of western blot to unravel the mechanism of regulation. To clarify the target of these drugs, we knocked down the endogenous LSD1 and AR using sh RNA in LNCa P cells.Results:(1)The suppression of prostate cancer cell(LNCa P) proliferation by JQ1 and HCI2509 is higher than DU145.(2)JQ1 and HCI2509 also induced G1 cell cycle arrest and apoptosis.(3) JQ1 and HCI2509 lead to the activation of tumor suppressor genes P21,P27 and the loss of function ofCyclin D1.(4) Our findings demonstrated that LSD1 expression was significantly higher in LNCa P than DU145.(5) JQ1 enhanced the suppression of HCI2509 to the endogenous AR.(6) Knockdown the endogenous AR didn't effect the cell proliferation inhibition rates of LNCa P induced by HCI2509 and JQ1.(7) Knockdown the endogenous LSD1 impair the cell proliferation inhibition rates of LNCa P induced by HCI2509 and JQ1.Conclusion: JQ1 enhanced the effect suppressed cell proliferation and induced apoptosis of HCI2509 in prostate cancer cells. This effect positively correlates with the expression of LSD1.Dislike the traditional therapy which regulate the androgen receptor to suppress the prostate cancer growth. In summary, HCI2509 and JQ1 effectively suppressed prostate cancer growth in vitro, and had strong efficacy via regulation of apoptosis. Further, human prostate cancers were found to different expression of LSD1 and BRD4. Therefore, our findings offer a novel potential therapeutic agent for prostate cancer.