硫利达嗪增敏食管癌细胞对放疗诱导凋亡的体内外研究
发布时间：2018-10-30 15:28
【摘要】：背景与目的放射治疗是目前治疗食管鳞状细胞癌(ESCC)的主要方法之一。然而由于肿瘤细胞放疗抵抗的存在,食管鳞癌的预后并没有明显改善。本实验主要研究抗精神类药物硫利达嗪对食管鳞癌细胞的放疗增敏效应。材料与方法以硫利达嗪与放疗单独或联合处理人食管癌细胞ECA-109和TE-1。MTT法检测增殖抑制效应,流式细胞术检测细胞周期及凋亡程度改变,蛋白印迹法分析p-PI3K、p-AKT、p-m TOR、Caspase-3、Caspase-9、Bax、Bcl-2、Bcl-xl、t Bid和PTEN的表达改变。以荷瘤小鼠模型评估体内硫利达嗪单独和联合放疗的疗效。结果相比单独处理组,硫利达嗪和放疗联合处理能显著降低食管鳞癌细胞的活性和存活率,联合处理可诱导食管癌细胞发生G0/G1期细胞周期阻滞,并使周期蛋白CDK4及cyclin D1的表达水平下调。硫利达嗪联合放疗可激活caspase-3/9促使食管癌细胞发生凋亡,同时伴随Bax、t Bid的上调及Bcl-2、Bcl-xl表达降低。联合处理还能明显抑制PI3k/AKT/m TOR通路及上调胞内PTEN水平。通过荷瘤小鼠模型验证硫利达嗪联合放疗的效果,联合处理组的小鼠的肿瘤生长速度明显延缓。结论硫利达嗪被可显著增加食管鳞癌细胞对放疗的敏感性,提示硫利达嗪可能是一种潜在的有前途的食管鳞癌放疗增敏剂。
[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.
【学位授予单位】：安徽医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.1
本文编号：2300396
[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.
【学位授予单位】：安徽医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R735.1
【参考文献】
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1 曹建忠;罗京伟;徐国镇;;红细胞生成素在肿瘤放疗中的研究现状[J];中华放射肿瘤学杂志;2006年04期
，本文编号：2300396
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