蛋白质翻译起始因子eIF-4Al与宫颈癌放疗敏感性的基础和临床研究

发布时间：2018-07-04 14:22

本文选题：宫颈癌 + 放疗敏感性　；参考：《复旦大学》2014年博士论文

【摘要】：目的：1.eIF-4A1、eIF-4E、eIF-4G1在宫颈癌的表达及临床意义；2.调控eIF-4A1表达对宫颈癌Siha、Hela细胞功能的影响；3.eIF-4A1对宫颈癌放疗敏感性的影响及机制。材料和方法：35例正常宫颈组织及137例宫颈癌患者的石蜡标本均来源于复旦大学附属肿瘤医院组织库。采用Siha、Hela细胞做为载体进行体外体内实验。实验方法包括CCK8试剂盒检测细胞增殖实验,Transwell检测细胞的迁移侵袭能力,流式细胞仪检测细胞凋亡和周期,克隆形成实验检测细胞的放疗敏感性,以及裸鼠皮下成瘤和放疗相关实验。Western blot实验进行相关的机制研究。结果：1.eIF-4A1、eIF-4E 和 eIF-4G1在正常宫颈组织中表达阴性,宫颈癌中高表达(阳性率大于80%)。eIF-4A1、eIF-4 E 和 eIF-4G1表达水平与患者的FIGO分期、组织病理学类型、盆腔淋巴结有无转移相关(P0.05)。放疗后eIF-4A1和eIF-4E表达变化和患者的放疗敏感性相关(P分别为0.029、0.012)。放疗后eIF-4A1表达降低的患者预后较好(P=0.002),并且是患者良好预后的独立影响因素(P=0.047)。2.抑制eIF-4A1表达可以抑制宫颈癌细胞的增殖、侵袭转移,促进细胞凋亡,延迟细胞放疗所致DSB损伤修复。3.体内体外实验证实,降低eIF-4A1表达可以增加宫颈癌的放疗敏感性。结论：放疗后eIF-4A1表达下降是宫颈癌良好预后的独立影响因素。eIF-4A1通过延迟放疗后DSB损伤修复增加宫颈癌的放疗敏感性。
[Abstract]:Objective to investigate the expression and clinical significance of eIF-4A1EIF-4EIF-4G1 in cervical carcinoma. Regulation of eIF-4A1 expression on the function of Siha-Hela cells in Cervical Cancer. 3. The effect of eIF-4A1 on the radiosensitivity of cervical cancer and its mechanism. Materials and methods paraffin specimens of 35 normal cervical tissues and 137 cervical cancer patients were collected from the tissue bank of tumor Hospital affiliated to Fudan University. Sihagne Hela cells were used as carriers for in vitro experiments. The methods included CCK8 kit and Transwell assay, flow cytometry to detect cell apoptosis and cell cycle, clone formation assay to detect the sensitivity of cell to radiotherapy, to detect cell migration and invasion ability, to detect cell apoptosis and cell cycle by flow cytometry. The mechanism of subcutaneous tumorigenesis and radiotherapy-related experiments in nude mice was studied by Western blot assay. Results 1. The expression of eIF-4A1eIF-4E and eIF-4G1 were negative in normal cervix, and the overexpression of eIF-4A1eIF-4E and eIF-4G1 in cervical carcinoma were correlated with Figo stage, histopathological type and pelvic lymph node metastasis (P0.05). The changes of eIF-4A1 and eIF-4E expression were correlated with the radiosensitivity of patients after radiotherapy (P = 0.029, 0.012, respectively). The patients with lower expression of eIF-4A1 after radiotherapy had a better prognosis (P0. 002) and were independent factors of good prognosis (P0. 047). 2. Inhibiting the expression of eIF-4A1 can inhibit the proliferation, invasion and metastasis of cervical cancer cells, promote apoptosis and delay the repair of DSB damage induced by radiotherapy. In vivo and in vitro experiments have shown that reducing the expression of eIF-4A1 can increase the radiosensitivity of cervical cancer. Conclusion: the decrease of eIF-4A1 expression after radiotherapy is an independent factor influencing the good prognosis of cervical cancer. EIF-4A1 increases the radiosensitivity of cervical cancer through DSB damage repair after delayed radiotherapy.
【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R737.33

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