本文選題：乳腺癌 + 缺氧�。� 參考：《中國病理生理雜志》2017年10期

【摘要】：目的:探討慢性缺氧應(yīng)激對人乳腺癌MCF-7細(xì)胞惡性生物學(xué)行為的影響及可能機(jī)制。方法:將人乳腺癌MCF-7細(xì)胞分為缺氧組(1%O_2、5%CO_2和94%N_2)和正常對照組(常氧)進(jìn)行培養(yǎng)。利用MTT法、CCK-8實(shí)驗(yàn)、細(xì)胞直接計(jì)數(shù)法及細(xì)胞侵襲和遷移實(shí)驗(yàn)對MCF-7細(xì)胞活力、增殖及侵襲和遷移能力進(jìn)行檢測;用軟瓊脂集落形成實(shí)驗(yàn)及Matrigel 3D培養(yǎng)技術(shù)檢測MCF-7細(xì)胞非錨定生長能力及極性改變情況;利用MCF-7細(xì)胞構(gòu)建裸鼠皮下種植瘤模型,檢測慢性缺氧應(yīng)激對體內(nèi)腫瘤生長及肺轉(zhuǎn)移的影響;利用倒置顯微鏡觀察MCF-7細(xì)胞形態(tài)改變;Western blot檢測低氧誘導(dǎo)因子1(hypoxia-inducible factor-1,HIF-1)和磷酸化的糖原合成酶激酶3β(glycogen synthase kinase-3β,GSK-3β)在缺氧環(huán)境下表達(dá)水平的改變,以及E-鈣黏連蛋白(E-cadherin)、N-鈣黏連蛋白(Ncadherin)、波形蛋白(vimentin)、基質(zhì)金屬蛋白酶3(matrix metalloproteinase-3,MMP-3)、MMP-9等上皮-間充質(zhì)轉(zhuǎn)化(epithelial-mesenchymal transition,EMT)相關(guān)蛋白的表達(dá)水平。結(jié)果:與正常對照組相比較,慢性缺氧組MCF-7細(xì)胞活力、增殖能力及侵襲遷移能力增強(qiáng),細(xì)胞非錨定生長能力提高且在3D培養(yǎng)系統(tǒng)更容易發(fā)生極性改變,呈現(xiàn)侵襲樣生長,體內(nèi)生長及轉(zhuǎn)移能力增強(qiáng);除了HIF-1被缺氧誘導(dǎo)表達(dá)升高外,GSK-3β呈現(xiàn)活化趨勢,且上皮樣標(biāo)志物E-cadherin蛋白表達(dá)水平明顯下降,而間充質(zhì)樣標(biāo)志物N-cadherin、vimentin、MMP-3和MMP-9蛋白表達(dá)水平明顯升高。結(jié)論:慢性缺氧應(yīng)激促進(jìn)了乳腺癌細(xì)胞惡性生物學(xué)行為,且其機(jī)制可能與EMT有關(guān)。
[Abstract]:Objective: to investigate the effect of chronic hypoxia stress on malignant biological behavior of human breast cancer MCF-7 cells and its possible mechanism. Methods: human breast cancer MCF-7 cells were divided into hypoxia group and normal control group. The viability, proliferation, invasion and migration of MCF-7 cells were detected by MTT assay, direct cell count and cell invasion and migration assay. Soft Agar colony forming test and Matrigel 3D culture were used to detect the unanchored growth ability and polarity change of MCF-7 cells, the subcutaneous tumor model of nude mice was constructed by MCF-7 cells, and the effects of chronic hypoxia stress on tumor growth and lung metastasis in vivo were examined. The morphological changes of MCF-7 cells were observed by inverted microscope. The expression of hypoxia inducible factor 1(hypoxia-inducible factor-1 (HIF-1) and phosphorylated glycogen synthase kinase 3 尾 -glycogen synthase kinase-3 尾 -GSK-3 尾 were detected by Western blot under hypoxia. The expression levels of E-cadherin, vimentin, 3(matrix metalloproteinase-3 and MMP-3MMP 9 in epithelial-mesenchymal transition (EMT9) were also found in Ecadherin (E-cadherin), vimentin (vimentin), matrix metalloproteinase-3 (MMP) and matrix metalloproteinase-3 (MMPs). Results: compared with the control group, the MCF-7 cell viability, proliferation and invasion and migration ability of chronic hypoxia group were increased, and the cell unanchored growth ability was increased. In 3D culture system, polarity changes were more likely to occur, showing invasive growth. The ability of growth and metastasis in vivo was enhanced, the expression of GSK-3 尾 was increased by hypoxia, and the expression level of E-cadherin protein decreased significantly, while the expression of N-cadherin protein MMP-3 and MMP-9 protein of mesenchymal marker N-cadherin protein increased significantly. Conclusion: chronic hypoxia stress promotes malignant biological behavior of breast cancer cells, and its mechanism may be related to EMT.
【作者單位】： 安徽中醫(yī)藥大學(xué);廈門大學(xué)第一附屬醫(yī)院超聲科;安徽醫(yī)科大學(xué);
【基金】：中國博士后科學(xué)基金第59批面上資助項(xiàng)目(No.2016M592037) 安徽省自然科學(xué)基金資助項(xiàng)目(No.1608085MH187)
【分類號】：R737.9

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