【摘要】：背景與目的放射治療是目前治療食管鱗狀細(xì)胞癌(ESCC)的主要方法之一。然而由于腫瘤細(xì)胞放療抵抗的存在,食管鱗癌的預(yù)后并沒(méi)有明顯改善。本實(shí)驗(yàn)主要研究抗精神類(lèi)藥物硫利達(dá)嗪對(duì)食管鱗癌細(xì)胞的放療增敏效應(yīng)。材料與方法以硫利達(dá)嗪與放療單獨(dú)或聯(lián)合處理人食管癌細(xì)胞ECA-109和TE-1。MTT法檢測(cè)增殖抑制效應(yīng),流式細(xì)胞術(shù)檢測(cè)細(xì)胞周期及凋亡程度改變,蛋白印跡法分析p-PI3K、p-AKT、p-m TOR、Caspase-3、Caspase-9、Bax、Bcl-2、Bcl-xl、t Bid和PTEN的表達(dá)改變。以荷瘤小鼠模型評(píng)估體內(nèi)硫利達(dá)嗪?jiǎn)为?dú)和聯(lián)合放療的療效。結(jié)果相比單獨(dú)處理組,硫利達(dá)嗪和放療聯(lián)合處理能顯著降低食管鱗癌細(xì)胞的活性和存活率,聯(lián)合處理可誘導(dǎo)食管癌細(xì)胞發(fā)生G0/G1期細(xì)胞周期阻滯,并使周期蛋白CDK4及cyclin D1的表達(dá)水平下調(diào)。硫利達(dá)嗪聯(lián)合放療可激活caspase-3/9促使食管癌細(xì)胞發(fā)生凋亡,同時(shí)伴隨Bax、t Bid的上調(diào)及Bcl-2、Bcl-xl表達(dá)降低。聯(lián)合處理還能明顯抑制PI3k/AKT/m TOR通路及上調(diào)胞內(nèi)PTEN水平。通過(guò)荷瘤小鼠模型驗(yàn)證硫利達(dá)嗪聯(lián)合放療的效果,聯(lián)合處理組的小鼠的腫瘤生長(zhǎng)速度明顯延緩。結(jié)論硫利達(dá)嗪被可顯著增加食管鱗癌細(xì)胞對(duì)放療的敏感性,提示硫利達(dá)嗪可能是一種潛在的有前途的食管鱗癌放療增敏劑。
[Abstract]:Background and objective radiotherapy is one of the main methods for the treatment of esophageal squamous cell carcinoma (ESCC). However, the prognosis of esophageal squamous cell carcinoma has not been significantly improved due to tumor cell radiotherapy resistance. The aim of this study was to study the radiosensitizing effect of tiridamine on esophageal squamous carcinoma cells. Materials and methods ECA-109 and TE-1.MTT were used to detect proliferation inhibition of human esophageal carcinoma cells treated with tiridazide alone or in combination with radiotherapy. Cell cycle and apoptosis were detected by flow cytometry and p-PI3K were analyzed by Western blot. The expression of p-AKT TOR,Caspase-3,Caspase-9,Bax,Bcl-2,Bcl-xl,t Bid and PTEN was changed. Tumor-bearing mice model was used to evaluate the efficacy of tiridazide alone and in combination with radiotherapy in vivo. Results compared with the single treatment group, the combination of tiridamine and radiotherapy could significantly reduce the activity and survival rate of esophageal squamous carcinoma cells, and the combined treatment could induce cell cycle arrest in the G0/G1 phase of esophageal cancer cells. The expression of cyclin CDK4 and cyclin D1 was down-regulated. Telidazide combined with radiotherapy could activate caspase-3/9 and induce apoptosis of esophageal carcinoma cells, accompanied by up-regulation of Bax,t Bid and decrease of Bcl-2,Bcl-xl expression. Combined treatment also inhibited PI3k/AKT/m TOR pathway and upregulated intracellular PTEN level. The tumor-bearing mice model was used to verify the effect of tiridazide combined with radiotherapy, and the tumor growth rate of the combined treatment group was significantly delayed. Conclusion tiridamine can significantly increase the sensitivity of esophageal squamous cell carcinoma cells to radiotherapy, suggesting that tiridamine may be a potential radiosensitizer for esophageal squamous cell carcinoma.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R735.1

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相關(guān)期刊論文 前1條

1 曹建忠;羅京偉;徐國(guó)鎮(zhèn);;紅細(xì)胞生成素在腫瘤放療中的研究現(xiàn)狀[J];中華放射腫瘤學(xué)雜志;2006年04期

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本文編號(hào)：2300396