本文關(guān)鍵詞： 苯并(a)芘 胃癌 增殖 侵襲 轉(zhuǎn)移　出處：《蘭州大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

【摘要】：目的胃癌是世界范圍內(nèi)最常見(jiàn)的惡性腫瘤之一,位居全球癌癥相關(guān)死亡原因的第三位。環(huán)境因素在胃癌的發(fā)生發(fā)展中發(fā)揮著不可忽視的作用,苯并(a)芘(benzo(a)pyrene,BaP)是廣泛存在于煎炸和煙熏食品以及香煙煙霧中的強(qiáng)致癌物質(zhì),其已被國(guó)際癌癥研究中心(International Agency for Research on Cancer,IARC)列為Ⅰ類致癌物質(zhì)�，F(xiàn)有研究表明,BaP可導(dǎo)致多個(gè)器官的癌癥發(fā)生并與肝癌、乳腺癌、肺癌等多種癌癥的發(fā)展密切相關(guān)。已有動(dòng)物實(shí)驗(yàn)表明,經(jīng)口給予BaP會(huì)導(dǎo)致小鼠胃癌前病變及胃癌,但其具體作用機(jī)制仍不清楚。因此,本實(shí)驗(yàn)旨在闡明BaP對(duì)胃癌SGC-7901及MNK-45細(xì)胞的增殖、侵襲轉(zhuǎn)移的影響及其具體機(jī)制,以期為環(huán)境因素對(duì)胃癌影響及防治工作提供實(shí)驗(yàn)依據(jù)。方法胃癌SGC-7901及MNK-45細(xì)胞暴露于不同濃度的BaP(如0.05,0.1,0.5,1,5μM)及溶劑對(duì)照0.1%二甲基亞砜(dimethyl sulphoxide,DMSO)中16-48 h。用CCK-8實(shí)驗(yàn)檢測(cè)不同濃度BaP對(duì)胃癌SGC-7901及MNK-45細(xì)胞增殖能力的影響。用transwell遷移實(shí)驗(yàn)檢測(cè)不同濃度BaP對(duì)胃癌SGC-7901及MNK-45細(xì)胞轉(zhuǎn)移及侵襲能力的影響。采用逆轉(zhuǎn)錄聚合酶鏈反應(yīng)(reverse transcription-polymerase chain reaction,RT-PCR)以及western blot檢測(cè)BaP作用下胃癌SGC-7901及MNK-45細(xì)胞內(nèi)致癌基因基質(zhì)金屬蛋白酶9(matrix metalloproteinase 9,MMP9)、c-myc的表達(dá)水平以及芳香烴受體(aryl hydrocarbon receptor,AHR)和ERK信號(hào)通路的傳導(dǎo)變化。然后用AHR拮抗劑白藜蘆醇(resveratrol,RSV)以及ERK通路拮抗劑U0126檢測(cè)AHR-MMP9/c-myc及ERK-MMP9/c-myc信號(hào)通路是否參與BaP誘導(dǎo)的細(xì)胞內(nèi)信號(hào)傳導(dǎo)過(guò)程。結(jié)果CCK-8實(shí)驗(yàn)表明相較于溶劑對(duì)照組,各不同劑量BaP實(shí)驗(yàn)組所檢測(cè)到的反映胃癌SGC-7901及MNK-45細(xì)胞增殖能力的OD值均明顯增加,且具有統(tǒng)計(jì)學(xué)差異。Transwell轉(zhuǎn)移及侵襲實(shí)驗(yàn)結(jié)果顯示遷移至下室的細(xì)胞計(jì)數(shù)后通過(guò)統(tǒng)計(jì)學(xué)分析表明各劑量實(shí)驗(yàn)組的細(xì)胞數(shù)與溶劑對(duì)照組比較有統(tǒng)計(jì)學(xué)差異。RT-PCR以及western blot檢測(cè)結(jié)果表明BaP可從mRNA和蛋白質(zhì)的水平促進(jìn)胃癌SGC-7901及MNK-45細(xì)胞內(nèi)MMP9和c-myc的表達(dá)。同時(shí)也可分別激活A(yù)HR和ERK信號(hào)通路,而AHR拮抗劑RSV和ERK拮抗劑U0126可分別抑制BaP誘導(dǎo)的MMP9和c-myc過(guò)表達(dá)。結(jié)論BaP可能通過(guò)促進(jìn)c-myc和MMP9的表達(dá)而增強(qiáng)胃癌SGC-7901及MNK-45細(xì)胞的增殖和轉(zhuǎn)移能力,并且BaP可通過(guò)激活A(yù)HR和ERK信號(hào)通路促進(jìn)胃癌細(xì)胞內(nèi)c-myc和MMP9的表達(dá)。
[Abstract]:Objective gastric cancer is one of the most common malignant tumors in the world, and it is the third leading cause of cancer-related death in the world. Environmental factors play an important role in the development of gastric cancer. Benzopyrene benzoa pyrene BaP) is a powerful carcinogen widely found in frying and smoking foods as well as cigarette smoke. It has been established by the International Agency for Research on Cancer. IARC) is classified as class 鈪，

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