Preliminary Study Of Mechanism Of Hedgehog Signaling Pathway In Prostate Cancer

Hh signaling pathway is a highly conserved system, which controls axial organ allelotaxy and plays a crucial role in embryonal growth and development of mammalian. This signaling pathway is also closely related with development and progression of human cancer. The signaling pathway was found in basal cell carcinoma, gastric cancer, pancreatic cancer, colon carcinoma, small cell lung cancer, breast cancer, ovarian cancer, endometrial cancer, esophageal cancers and so on.Prostate cancer(PCa)is also belong to endoderm tumor, and whether Hh signaling pathway plays an important role in PCA? In this study, we try to research mechanism of Hh signaling pathway in prostate cancer by follow experiments.Part1Signification of expression of hedgehog signaling pathway transcription protein GIi-1in PCAObjctive:Detect prostate cancer specimens were and find out whether the expression of Gli-1was existing in the prostate cancer.Methods:Immunohistochemistry was used to examine the expression of Gli1protein in15cases of human prostate cancer, then we analyzed the associativity among expression of Gli1, and clinical pathological stage in prostate cancer tissues.Results:The expression of Gli-1protein on prostate cancer tissue was much more than cancer adjacent tissues. and expression of Gli-1was related to the pathological stage of prostate cancerConclusion:The expression of Gli-1was related to the pathological stage of prostate cancer, and prove Hh singnaling plays an important role in the development of prostate cancer. Part2Mechanism of hedgehog signaling pathway in prostate cancer Objctive:We investigated the molecular biology molecule mechanism of Hh signaling pathway on MMP-9、VEGF correlated with invasion and metastasis, and mechanism of Hh signaling activation of human prostate cancer Du145cells after Hh signaling pathway being blocked with cyclopamine.Methods:Cultured DU145cells,blocking it’s Hh signaling pathway by cyclopamine,and Transwell chamber experiments was used to examine the change of Du145invasiveness; Real-time PCR was used to examine the expression of Shh、Gli-1、MMP-9、VEGF mRNA; and Immunohistochemistry was uesed to examine the expression of Shh、 Gli-1、MMP-9、VEGF protein.Results:After Blocking Hh signaling pathway, The invasiveness of Du145was decreased, and the expression of Shh、Gli-1、MMP-9、 VEGF mRNA、protein was also decreased.Conclusion:1. After Blocking Hh signaling pathway by cyclopamine, The invasiveness Du145was decreased.2.After Blocking Hh signaling pathway by cyclopamine, SHH、GLI-1mRNA and protein was also decreased, which prove the Hh signaling in Du145maybe activitied as an autocrine manner.3.After Blocking Hh signaling pathway by cyclopamine,The invasiveness of Du145was decreased,and Hh signaling maybe control the Du145invasiveness by regulat the expression of MMP-9、VEGF,MMP-9、VEGF maybe the target gene of Hh signaling.