Effect Of Ethyl Pyruvate On Prostate Cancer And Mechanism Study

Prostate cancer is the most commonly malignant tumor in American men.proportion of prostate cancer in newly diagnosed male cancer patients is around 1/5.The second most common cause of cancer death is prostate cancer in men,second to lung cancer.Compared with western countries,the incidence and mortality of prostate cancer in China is relatively low,but with the economic development,westernization of lifestyle and dietary changes in the structure,population aging and improving health-care level,the incidence of prostate cancer growth is also rapid in the past 10 years.Prostate cancer has become a serious urinary tract disease that seriously affects male health in our country,but the treatment of prostate cancer is still a difficult problem.Ethyl pyruvate(EP)is a stable aliphatic ester derived from pyruvic acid that has been shown to suppress inflammation,mitigate redox-mediated cellular damage,and exert immunoregulatory and neuroprotective effects.Ethyl pyruvate can effectively reduce the serum levels of inflammatory factors such as HMGB1,TNF-a,NF-KB,interleukin-6 and so on.It's anti-tumor role has attracted the attention of researchers.It has been proved that ethyl pyruvate exert anticancer effect on pancreatic cancer,gallbladder cancer,gastric cancer,leukemia and other malignant tumor.Ethyl pyruvate can inhibite cell proliferation,induce cell apoptosis and block cell cycle.However,the molecular basis for these effects is not well understood,and they have not been investigated in the context of PCa.The effect of ethyl pyruvate on the proliferation of prostate cancer cells was detected by CCK-8 experiment and colony formation assay.The effect of ethyl pyruvate on the migration and invasion of prostate cancer cells was detected by cell scratch healing test and transwell invasion assay.The effects of ethyl pyruvate on the cell cycle distribution and apoptosis of prostate cancer cells were detected by flow cytometry.In addition,Tumor sphere formation assay was used to detect its effect on the prostate cancer stem cells phenotype,and the tumor inhibitory effect of ethyl pyruvate in vivo was detected by constructing a subcutaneous xenograft tumor in nude mice.The effect of ethyl pyruvate combination with enzalutamide on the proliferation was further examined.At last,Western blotting was used to detect change of molecular signaling pathway in prostate cancer cells treated with ethyl pyruvate.Results:1.The ethyl pyruvate inhibits proliferation in prostate cancer cells in vitro and in vivo;2.The ethyl pyruvate leads to cell cycle arrest and induces apoptosis in prostate cancer cell;3.The ethyl pyruvate inhibits the migration and invasion of prostate cancer4.The ethyl pyruvate suppresses epithelial mesenchymal transition and cell stem phenotype5.The ethyl pyruvate may exert anti-tumor effect by negatively regulating AKT/NF-KB pathway;6.The ethyl pyruvate sensitizes enzalutamide inhibition on the proliferation of castration resistant prostate cancer...