Hepcidin And Iron Metabolism In The Mechanism Of On Prostate Cancer Progression

Prostate cancer is a common tumor in men. The study suggests that iron metabolismplays an important role in prostate cancer growth, angiogenesis and metastasis. Iron isnecessary for body to maintain the function, participate the growth of body. Thedevelopment of tumor increases the need for iron, iron is considered to maintain thegrowth of tumor.Iron metabolism affect tumor’s development, and reduce iron metabolismis considered to be anti-tumor. The study show that through iron metabolism reduceintracellular iron,can influence tumor growth,be used as new anti-tumor therapy.Hepcidin plays an important role in the regulation of iron metabolism from liver cells.It plays a central role that reduces the intracellular release of free iron, and reduces ironabsorption by duodenum, negatively regulate iron metabolism. Previous studies exploredthe mechanism of Hepcidin by animal models and patients with abnormal iron metabolism.Hepcidin gene knockout mice can occur iron overload, and overexpress Hepcidin canoccur iron deficiency anemia. Hepcidin that expressed in tumor affected by many factors,many scholars’ attention attracted by iron metabolism in tumor. Hepcidin adjust itsreceptor-Ferroportin, transports intracellular iron to extracellular, produces lowexpression of Ferroportin and high expression of intracellular iron, make tumor cells moreaggressiver. The role of Hepcidin in prostate cancer has not been studied.We study Hepcidin expressed in prostate cancer tissues, Hepcidin interference inprostate cancer cells,and Hepcidin regulate iron metabolism in prostate cancer cells.Research into three parts: Part I: Hepcidin and prostate cancer in clinical researchObjective: To study Hepcidin and iron metabolism relationship in clinical research ofprostate cancer patients.Methods: Enzyme-linked immunosorbent assay (ELISA) determinate serumHepcidin,IL-6,sTfR and BMP6in25patients of prostate cancer with bone metastases,30patients of prostate cancer without bone metastases,and30patients in normal controlgroup;and detect all peoples’ Hemoglobin; and all tissue samples detect the expression ofFerroportin by immunohistochemistry, analysis with grading and staging of prostatecancer correlate to Ferroportin, research clinical significance of Hepcidin associated withprostate cancer.Results: Serum Hepcidin significantly increased in prostate cancer patients with bonemetastases than patients of prostate cancer without bone metastases and common controlgroup, was statistically difference (P <0.05); and Hepcidin correlated with IL-6, BMP6positively, sTfR was correlated with negatively; in prostate cancer tissue, Ferroportinexpression was significantly reduced than benign prostatic hyperplasia, differences aresignificantly, Ferroportin expression was negatively correlation with severity of prostatecancer.Conclusion:In Prostate cancer patients,Hepcidin expression increased, Ferroportinexpression decreased, may be related to the patients’ inflammatory, the degreement ofbone metastasis.Hepcidin may as a indicator with progress of prostate cancer, to providenew diagnosis of prostate cancer in clinical judgment.Part II: Hepcidin regulate prostate cancer cells in biological functionObjective: To investigate Hepcidin expressed in prostate cancer cells, Si-Hepcidin effecton prostate cancer cells in proliferation, migration and apoptosis of biology functions.Methods: Detect Hepcidin expressed in prostate cancer cells; small interfering RNAHepcidin in PC3and DU145, research Si-Hepcidin prostate cancer cells of proliferation,migration, cell cycles, anti-apoptotic ability; and Si-Hepcidin PC3implanted in nude mice xenografts, analysis with Si-Hepcidin PC3differences in tumor growth of prostatecancer as control group in the body.Results: Hepcidin expressed higher in prostate cancer cells compared than normal prostatecells,significantly difference (P <0.05); After Si-Hepcidin, prostate cancer cells weakenedin proliferation, migration, anti-apoptotic ability compared with control group andnegative group, significantly difference (P <0.05); Si-Hepcidin prostate cancer cells makevolume in nude mice smaller than the control group, significantly difference (P <0.05).Conclusions: Hepcidin was highly expressed in prostate cancer cells; Si-Hepcidin effecton prostate cancer cells reduced express in proliferation, migration, cell cycles,anti-apoptotic ability; Si-Hepcidin effect on prostate cancer cells cause tumor formationsmaller than control group, indicate Hepcidin may produce iron metabolism signalingpathways regulate of prostate cancer cells,Hepcidin was played an important role inprostate cancer that progression of growth and invasion.Part III: Exogenous Hepcidin regulate prostate cancer cells of ironmetabolism in molecular mechanismObjective: To investigate Hepcidin expressed in iron metabolism of signaling pathways inprostate cancer cells, through exogenous Hepcidin effect on prostate cancer cells changedbiological functions, and research in molecular mechanisms of iron metabolism, indicateHepcidin impact on progression in prostate cancer cells through the regulation of ironmetabolism.Methods: Cultured PC3and Si-Hepcidin PC3, using Real-Time PCR and Western-blotdetect Ferroportin,using immunofluorescence detect intracellular iron; Si-Hepcidin PC3adding to exogenous Hepcidin500nm, observed on prostate cancer cells proliferation,migration and anti-apoptosis ability to changed with no exogenous Hepcidin group;Real-Time PCR and Western-blot detect Ferroportin, immunofluorescence measureintracellular iron after Si-Hepcidin PC3adding to exogenous Hepcidin500nm,compared with no exogenous Hepcidin group.Results: Si-Hepcidin PC3expressed Ferroportin more than PC3, reduced intracellular ironcompared with PC3, significantly difference (P <0.05); add to exogenous Hepcidin500nm,+Hepcidin PC3group enhanced proliferation,migration and anti-apoptosis capacitywith-Hepcidin PC3group, significantly difference (P <0.05); add to exogenous Hepcidin,+Hepcidin PC3group expressed litter Ferroportin than-Hepcidin PC3group, intracellulariron increased, significantly difference (P <0.05).Conclusion: Hepcidin regulate the expression of Ferroportin and intracellular iron inprostate cancer cells.Hepcidin regulate prostate cancer cells of proliferation, migration andanti-apoptosis ability.Hepcidin may as a new therapeutic target in prostate cancerprogression, Hepcidin regulate on prostate cancer by iron metabolism, play an activelyclinical treatment.