本文關(guān)鍵詞：硼替佐米通過抑制HIF-1α的表達(dá)對乏氧宮頸癌細(xì)胞株產(chǎn)生放療增敏作用的研究　出處：《蚌埠醫(yī)學(xué)院》2015年碩士論文　論文類型：學(xué)位論文

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【摘要】：本研究旨在探討硼替佐米對于宮頸癌的放療增敏作用及可能的機(jī)制。宮頸癌是最常見的的婦科惡性腫瘤之一,放射治療是其主要治療方法,目前仍有相當(dāng)比例的患者存在放射治療抵抗。實(shí)體瘤中乏氧細(xì)胞約占10%-50%,對放射線有較強(qiáng)的抵抗力。有文獻(xiàn)報(bào)道女性宮頸癌中腫瘤氧合好的患者放療后無復(fù)發(fā)生存率明顯高于氧合差的患者。硼替佐米能夠特異性抑制哺乳動(dòng)物細(xì)胞內(nèi)26S蛋白酶體的類凝乳胰蛋白酶活性,通過降解調(diào)節(jié)蛋白,產(chǎn)生抗增殖、促凋亡、抗血管生成,從而起到抑制腫瘤活性的作用。分別把常氧和乏氧兩種狀態(tài)下的宮頸癌細(xì)胞系HeLa細(xì)胞和SiHa細(xì)胞分為對照組、放射治療組、藥物組(低濃度、高濃度)和放射治療聯(lián)合藥物組。通過CCK8實(shí)驗(yàn)檢測細(xì)胞增殖能力,進(jìn)而選擇藥物濃度；通過克隆形成實(shí)驗(yàn)比較集落形成數(shù)量,得到常氧狀態(tài)和乏氧狀態(tài)下硼替佐米對于兩種細(xì)胞的放射增敏比(SER)；隨后通過流式細(xì)胞術(shù)檢測細(xì)胞凋亡；免疫熒光實(shí)驗(yàn)檢測DNA雙鏈斷裂(DSB); Western blot實(shí)驗(yàn)檢測HIF-1α、PARP-1和Caspase-3、8、9的表達(dá)情況。數(shù)據(jù)統(tǒng)計(jì)分析表明,納摩爾水平的硼替佐米對常氧和乏氧兩種狀態(tài)下的宮頸癌細(xì)胞均具有放射治療增敏作用。Western blot實(shí)驗(yàn)表明該藥物能抑制HIF-la的表達(dá)、促進(jìn)與凋亡相關(guān)的Caspase-3、8、9的激活、增加與DBS相關(guān)的PARP-1裂解。因此,硼替佐米可能是潛在的宮頸癌放射治療增敏劑。
[Abstract]:The purpose of this study was to investigate the radiosensitizing effect of bortezomil on cervical cancer and its possible mechanism. Cervical cancer is one of the most common gynecological malignancies and radiotherapy is the main treatment. At present, there is still a considerable proportion of patients with radiotherapy resistance. The proportion of hypoxic cells in solid tumors is about 10-50%. It has been reported that the recurrence free survival rate of female cervical cancer patients with good oxygenation after radiotherapy is significantly higher than that of patients with poor oxygenation. Bortezomil can specifically inhibit mammalian cell 2. The chymotrypsin activity of 6s proteasome. Through the degradation of regulatory proteins, the production of anti-proliferation, apoptosis, anti-angiogenesis. The cervical cancer cell line HeLa and SiHa were divided into control group, radiotherapy group and drug group (low concentration). CCK8 assay was used to test the cell proliferation ability, and then the drug concentration was selected. By comparing the number of colony formation with clone formation experiments, the radiosensitization ratio of Bortezomil to the two kinds of cells was obtained in normoxic and hypoxic state. Apoptosis was detected by flow cytometry. The double strand breaks of DNA were detected by immunofluorescence assay. Western blot assay was used to detect the expression of HIF-1 偽 -PARP-1 and Caspase-3 and Caspase-3, and the statistical analysis showed that the expression of PARP-1 and Caspase-3 was detected by statistical analysis. Bortezomil at nanomolor level can sensitize cervical cancer cells in both normoxic and hypoxic states by radiotherapy. Western. Blot assay showed that the drug could inhibit the expression of HIF-la. The activation of apoptosis-related Caspase-3 and caspase-8, and the increase of PARP-1 cleavage associated with DBS were promoted. Therefore, bortezomil may be a potential radiosensitizer for cervical cancer.
【學(xué)位授予單位】：蚌埠醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R737.33

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