Hedgehog信号通路调控Twist1表达促进肝癌细胞侵袭转移分子机制研究-内科学（消化系病）专业业论文.docx

第三军医大学博士学位论文Mg 第三军医大学博士学位论文 Mg miiligram 毫克 FCS fetal calf serum 胎牛血清 EMT Epithelial-mesench)7mal transition 上皮．间质转化 RNase Ribonuclease RNA酶 RNasin Ribonuclease inhibitor RNA酶抑制剂 HE Haematoxylin-eosin 苏木素．伊红 HRP horseradish peroxidase 辣根过氧化物酶 2 万方数据 第三军医大学博士学位论文Mechanism 第三军医大学博士学位论文 Mechanism study of Hedgehog signaling regulating Twistl expression and promoting hepatic cellular cancer invasion and metastasis Abstract Baekground： Primary hepatocellular carcinoma(HCC)is one of common human malignancies．It is the third most deadly and the fifth most common malignancy worldwide，with an estimation of 600000 new per year．Surgical removal and liver transplantation remain are the most effective therapy for HCC．Although various adjuvant approaches to treat non-resectable HCC are available，the efficacy and three—year survival rate(30-40％)are not promising．Invasion and metastases are two fundamental properties of the malignancy,which determine the prognosis of HCC patients，especially poorly differentiated HCC．Thus，seeking molecular targets that could improve the treatment outcome is intriguing． The invasive mechanism of hepatocellular carcinoma is still not clear．The existing theory of tumorigenesis，such as genetic changes，including the activation of proto’oncogenes， gene deletion or mutation，the reactivation of telomerase activity and epigenetic abnormalities， Can not be the comprehensive explanation of molecular mechanisms to metastasis and recurrence of hepatocellular carcinoma．The present study showed that tumor cells have obvious heterogeneity．In the same tumor cells，many cells showed obvious inconsistency in genotype and molecular phenotype，allowing the the differences in growth，invasion and metastasis ability of these tumor cells，and their sensitivity to drugs． The hedgehog(nh)signaling pathway is highly conserved，and has a crucial role in embryogenesis，adult tissue homeostasis and carcinogenesis．Transcription factors Gli-1，Gli-2 and Gli．3 constitute the Gli family