橙皮苷對TGF-β1誘導(dǎo)的A549非小細(xì)胞肺癌細(xì)胞上皮間質(zhì)轉(zhuǎn)化的影響
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本文選題:橙皮苷 切入點:非小細(xì)胞肺癌細(xì)胞 出處:《中國醫(yī)院藥學(xué)雜志》2017年08期 論文類型:期刊論文
【摘要】:目的:探討橙皮苷對轉(zhuǎn)化生長因子-β1(transforming growth factor-β1,TGF-β1)誘導(dǎo)的人非小細(xì)胞肺癌細(xì)胞上皮-間質(zhì)轉(zhuǎn)化的影響。方法:以A549人非小細(xì)胞肺癌細(xì)胞系作為研究對象。用MTT法,分別檢測橙皮苷對正常培養(yǎng)條件或TGF-β1刺激下細(xì)胞增殖的影響。應(yīng)用2種方法評估橙皮苷對TGF-β1刺激條件下A549細(xì)胞的上皮間質(zhì)轉(zhuǎn)化:圓形度值定量評估細(xì)胞的形態(tài)變化;雙抗體夾心酶聯(lián)免疫吸附法(enzyme linked-immuno-sorbent assay,ELISA)檢測上皮細(xì)胞鈣黏蛋白(E-cadherin,E-cad)、ɑ-平滑肌肌動蛋白(ɑ-smooth muscle actin,ɑ-SMA)、基質(zhì)金屬蛋白酶抑制因子-1(tissue inhibitors of metalloproteinases-1,TIMP-1)和基質(zhì)金屬蛋白酶-9(metallopreoteinases-9,MMP-9)水平。結(jié)果:0~40μmol·L-1的橙皮苷對正常培養(yǎng)條件或TGF-β1刺激后A549細(xì)胞的增殖沒有顯著影響。5 ng·mL-1 TGF-β1能夠誘導(dǎo)A549細(xì)胞的上皮間質(zhì)轉(zhuǎn)化:由上皮特征的鋪路石狀的細(xì)胞形態(tài)轉(zhuǎn)化為梭形形態(tài),圓形度值減少;E-cad分泌量減少和ɑ-SMA合成量增加。另外,MMP-9分泌量增加,MMP-9/TIMP-1比值增加。在細(xì)胞出現(xiàn)形態(tài)改變后,應(yīng)用橙皮苷(20μmol·L-1或40μmol·L-1)能夠降低ɑ-SMA、MMP-9水平和MMP-9/TIMP-1比值,增加E-cad水平,對細(xì)胞的圓形度值沒有影響。結(jié)論:橙皮苷減輕TGF-β1誘導(dǎo)的非小細(xì)胞肺癌細(xì)胞的上皮間質(zhì)轉(zhuǎn)化程度,對非小細(xì)胞肺癌的轉(zhuǎn)移和擴散有一定的抑制作用。
[Abstract]:Objective: to investigate the effect of hesperidin on the epithelial-interstitial transformation of human non-small cell lung cancer cells induced by transforming growth factor- 尾 1 (TGF- 尾 1). Methods: A549 human non-small cell lung cancer cell line was used as the study object. The effects of hesperidin on the proliferation of A549 cells stimulated by TGF- 尾 1 or normal culture were determined. The epithelial mesenchymal transformation of A549 cells stimulated by hesperidin was evaluated by two methods: the roundness value was used to quantitatively evaluate the morphological changes of A549 cells. Enzyme linked immunosorbent assay (Elisa) was used to detect E-cadherin, smooth muscle actin, matrix metalloproteinase-1 inhibitors of metalloproteinases-1 and metalloproteinase-9 metallopreoteines-9MMP-9 in epithelial cells. Results the level of hesperidin was 40 渭 mol 路L-1. The proliferation of A549 cells stimulated by normal culture condition or TGF- 尾 1 had no significant effect on the proliferation of A549 cells. 5ng 路mL-1 TGF- 尾 1 could induce the epithelial interstitial transformation of A549 cells. In addition, the secretion of MMP-9 was increased and the ratio of MMP-9 / TIMP-1 was increased. After the morphological change of cells, the level of MMP-9 and the ratio of MMP-9/TIMP-1 were decreased and the level of E-cad was increased after the application of hesperidin 20 渭 mol 路L -1 or 40 渭 mol 路L -1). Conclusion: hesperidin can reduce the degree of epithelial mesenchymal transformation induced by TGF- 尾 1 and inhibit the metastasis and diffusion of NSCLC.
【作者單位】: 河南中醫(yī)藥大學(xué);呼吸疾病診療與新藥研發(fā)河南省協(xié)同創(chuàng)新中心;河南中醫(yī)藥大學(xué)第一附屬醫(yī)院;河南中醫(yī)藥研究院附屬醫(yī)院;
【基金】:國家自然科學(xué)基金項目(編號:81473650) 河南省高等學(xué)校重點科研項目計劃(編號:16A360002)
【分類號】:R734.2
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