目的:本課題研究擬以結(jié)腸癌細(xì)胞和構(gòu)建結(jié)腸癌耐藥細(xì)胞模型為基礎(chǔ),借助分子生物學(xué)及細(xì)胞生物學(xué)等先進(jìn)技術(shù),通過(guò)體外實(shí)驗(yàn)探討氧化苦參堿對(duì)結(jié)腸癌細(xì)胞和結(jié)腸癌耐藥細(xì)胞中TGF-β1/P38/PAI-1信號(hào)通路的干預(yù)作用,同時(shí)探索結(jié)腸癌上皮間質(zhì)化（Epithelial-mesenchymal transition,EMT）對(duì)結(jié)腸癌耐藥轉(zhuǎn)移的作用機(jī)制,并以此來(lái)闡明氧化苦參堿逆轉(zhuǎn)結(jié)腸癌EMT改變的分子機(jī)制及氧化苦參堿的抗腫瘤效用,為逆轉(zhuǎn)結(jié)腸癌多藥耐藥提供新的研究方向。材料與方法:1.檢測(cè)氧化苦參堿對(duì)于結(jié)腸癌細(xì)胞EMT的作用及遷移能力的影響。1.1對(duì)HT-29細(xì)胞和RKO細(xì)胞隨機(jī)分組,以正常結(jié)腸上皮細(xì)胞FHC細(xì)胞作為對(duì)照組。使用Western blots方法分別檢測(cè)各組細(xì)胞的EMT的相關(guān)標(biāo)志物,包括上皮細(xì)胞標(biāo)志物鈣粘附蛋白E（E-cadherin）和間充質(zhì)細(xì)胞標(biāo)志物α平滑肌肌動(dòng)蛋白（Alpha-smooth muscle actin,α-SMA）、纖連蛋白（fibronectin,FN）、纖溶酶原激活物抑制劑-1（Plasminogen Act ivat inhibitor-1,PAI-1）在內(nèi)的蛋白表達(dá)... 

【文章來(lái)源】：遼寧中醫(yī)藥大學(xué)遼寧省

【文章頁(yè)數(shù)】：110 頁(yè)

【學(xué)位級(jí)別】：博士

【部分圖文】：

結(jié)腸癌細(xì)胞發(fā)生EMT改變

.氧化苦參堿分子結(jié)構(gòu)（oxymatrinere 2. The molecular structure of oxy氧化苦參堿對(duì) RKO 細(xì)胞增殖的抑制ect of oxymatrine on the proliferatio24 h 48 h 4.07±1.39 4.64±2.45 6.39±2.17 7.76±4.3 11.48±2.8118.22±5.18a28.91±1.1a38.22±3.86a46.75±5.23a51.05±5.67a55.51±2.6a63.34±7a69.74±3.19a74.63±3.92a85.88±3.59a87.74±3.02a組 (OM 0 mg/mL).

圖 2.氧化苦參堿分子結(jié)構(gòu)（oxymatrine，OM）Figure 2. The molecular structure of oxymatrine.表 1 氧化苦參堿對(duì) RKO 細(xì)胞增殖的抑制率(%)Table 1. The inhibitory effect of oxymatrine on the proliferation inhibition of RKOM(mg/mL) 24 h 48 h 72 h0.125 4.07±1.39 4.64±2.45 5.46±1.320.25 6.39±2.17 7.76±4.3 11.54±6.120.5 11.48±2.8118.22±5.18a25.43±2.88a128.91±1.1a38.22±3.86a39.01±4.01a246.75±5.23a51.05±5.67a51.75±0.75a455.51±2.6a63.34±7a67.94±2.7a869.74±3.19a74.63±3.92a74.56±3.74a2085.88±3.59a87.74±3.02a90.33±2.28aaP < 0.05 vs. 對(duì)照組 (OM 0 mg/mL).

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