紫苏醇通过Notch信号通路抑制肝癌细胞侵袭和转移的实验研究
本文选题：紫苏醇 + 肝细胞肝癌 ； 参考：《南京医科大学》2016年博士论文
【摘要】：肝细胞肝癌是常见的消化系统恶性肿瘤,虽然治疗方法不断改进,仍是第三位常见致死性恶性肿瘤。肝癌死亡率居高不下的主要原因是肝癌的复发及肝内外转移。肝癌细胞转移,主要是侵袭和迁移的过程,主要包括肝癌细胞活动性增强,细胞之间粘附性降低。紫苏醇是一种单萜类天然抗癌物质,已经证实对多种肿瘤有效。现已证明,Notch信号通路不仅参与生物个体的生长发育,还参与肿瘤的不同发展过程,与肝癌的侵袭过程相关。本实验主要从研究紫苏醇对肝细胞肝癌的治疗作用及作用机制两方面进行研究,在分子机制水平为紫苏醇治疗肝癌提供理论基础。紫苏醇抑制肝细胞癌细胞株侵袭和迁移的研究。用划痕实验和Transwell实验对肝细胞癌细胞株HepG2, SMMC-7721,MHCC97H和人肝细胞株HL-7702进行对照研究,显示肝癌细胞株侵袭和迁移水平明显高于正常细胞,紫苏醇可以显著抑制肝癌细胞株的侵袭和迁移能力。应用RT-PCR技术检测Notch信号通路下游基因HES1, HES5 and HEY1的mRNA水平,结果提示肝细胞肝癌HES1,HES5 and HEY1的mRNA水平较正常肝细胞明显升高(P0.05),应用紫苏醇后mRNA水平显著下降(P0.05)。同时用Western Blot检测N1ICD、Snail和E-cadherin的表达。结果显示：在肝细胞肝癌中,N1ICD和Snail的表达明显增加,而E-cadherin的表达明显减少(P0.05),应用紫苏醇后N1ICD和Snail的表达明显下降,E-cadherin的表达明显增加(P0.05)。提示紫苏醇可以通过调控Notch信号通路抑制肝细胞肝癌的迁移能力。E-cadherin的表达受Snail的调控。体外成瘤实验显示紫苏醇可以在体内抑制肿瘤的生长。结论：紫苏醇在抑制肝细胞肝癌的侵袭和转移中发挥重要作用,可能的机制是通过抑制Notch信号通路的活性及增加被Snail调控的E-cadherin表达。
[Abstract]:Hepatocellular carcinoma (HCC) is a common malignant tumor of digestive system. The main cause of high mortality of liver cancer is the recurrence and metastasis of liver cancer. The metastasis of hepatoma cells mainly involves the process of invasion and migration, including the increase of the activity of hepatoma cells and the decrease of adhesion between hepatoma cells. Perilla alcohol is a monoterpene natural anticancer substance, which has been proved to be effective in many kinds of tumors. It has been proved that Notch signaling pathway is involved not only in the growth and development of biological individuals, but also in the different processes of tumor development, which is related to the invasion of liver cancer. In this study, the therapeutic effect and mechanism of perilla alcohol on hepatocellular carcinoma (HCC) were studied in order to provide a theoretical basis for the treatment of hepatocellular carcinoma with perilla alcohol at the molecular level. Study on inhibition of invasion and Migration of Hepatocellular carcinoma Cell Line by Peritol. A comparative study was carried out between HepG2, SMMC-7721 MHCC97H and HL-7702 by scratch test and Transwell test. The results showed that the invasion and migration level of HCC cell line was significantly higher than that of normal cell line. Perilla alcohol can significantly inhibit the invasion and migration of hepatoma cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA levels of HES1 and HES5 and HEY1 downstream genes in Notch signaling pathway. The results showed that the mRNA level of HES1 and HEY1 in HCC was significantly higher than that in normal hepatocytes (P0.05). The expression of Snail and E-cadherin were detected by Western blot. The results showed that the expression of N1ICD and Snail was significantly increased in hepatocellular carcinoma, but the expression of E-cadherin was significantly decreased (P0.05), and the expression of N1ICD and Snail was significantly decreased (P0.05). It is suggested that perilla alcohol can inhibit the migration ability of hepatocellular carcinoma by regulating Notch signaling pathway. E-cadherin expression is regulated by Snail. In vitro tumorigenesis test showed that perilla alcohol can inhibit tumor growth in vivo. Conclusion: Peritol plays an important role in inhibiting the invasion and metastasis of hepatocellular carcinoma by inhibiting the activity of Notch signaling pathway and increasing the expression of E-cadherin regulated by Snail.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.7
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