本文選題：紫蘇醇 + 肝細(xì)胞肝癌�。� 參考：《南京醫(yī)科大學(xué)》2016年博士論文

【摘要】：肝細(xì)胞肝癌是常見的消化系統(tǒng)惡性腫瘤,雖然治療方法不斷改進(jìn),仍是第三位常見致死性惡性腫瘤。肝癌死亡率居高不下的主要原因是肝癌的復(fù)發(fā)及肝內(nèi)外轉(zhuǎn)移。肝癌細(xì)胞轉(zhuǎn)移,主要是侵襲和遷移的過程,主要包括肝癌細(xì)胞活動(dòng)性增強(qiáng),細(xì)胞之間粘附性降低。紫蘇醇是一種單萜類天然抗癌物質(zhì),已經(jīng)證實(shí)對(duì)多種腫瘤有效。現(xiàn)已證明,Notch信號(hào)通路不僅參與生物個(gè)體的生長發(fā)育,還參與腫瘤的不同發(fā)展過程,與肝癌的侵襲過程相關(guān)。本實(shí)驗(yàn)主要從研究紫蘇醇對(duì)肝細(xì)胞肝癌的治療作用及作用機(jī)制兩方面進(jìn)行研究,在分子機(jī)制水平為紫蘇醇治療肝癌提供理論基礎(chǔ)。紫蘇醇抑制肝細(xì)胞癌細(xì)胞株侵襲和遷移的研究。用劃痕實(shí)驗(yàn)和Transwell實(shí)驗(yàn)對(duì)肝細(xì)胞癌細(xì)胞株HepG2, SMMC-7721,MHCC97H和人肝細(xì)胞株HL-7702進(jìn)行對(duì)照研究,顯示肝癌細(xì)胞株侵襲和遷移水平明顯高于正常細(xì)胞,紫蘇醇可以顯著抑制肝癌細(xì)胞株的侵襲和遷移能力。應(yīng)用RT-PCR技術(shù)檢測(cè)Notch信號(hào)通路下游基因HES1, HES5 and HEY1的mRNA水平,結(jié)果提示肝細(xì)胞肝癌HES1,HES5 and HEY1的mRNA水平較正常肝細(xì)胞明顯升高(P0.05),應(yīng)用紫蘇醇后mRNA水平顯著下降(P0.05)。同時(shí)用Western Blot檢測(cè)N1ICD、Snail和E-cadherin的表達(dá)。結(jié)果顯示：在肝細(xì)胞肝癌中,N1ICD和Snail的表達(dá)明顯增加,而E-cadherin的表達(dá)明顯減少(P0.05),應(yīng)用紫蘇醇后N1ICD和Snail的表達(dá)明顯下降,E-cadherin的表達(dá)明顯增加(P0.05)。提示紫蘇醇可以通過調(diào)控Notch信號(hào)通路抑制肝細(xì)胞肝癌的遷移能力。E-cadherin的表達(dá)受Snail的調(diào)控。體外成瘤實(shí)驗(yàn)顯示紫蘇醇可以在體內(nèi)抑制腫瘤的生長。結(jié)論：紫蘇醇在抑制肝細(xì)胞肝癌的侵襲和轉(zhuǎn)移中發(fā)揮重要作用,可能的機(jī)制是通過抑制Notch信號(hào)通路的活性及增加被Snail調(diào)控的E-cadherin表達(dá)。
[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.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.7

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