發(fā)布時(shí)間：2018-12-12 20:10

【摘要】：采用氣相色譜-質(zhì)譜(GC-MS)的代謝組學(xué)技術(shù)研究人卵巢癌紫杉醇耐藥細(xì)胞A2780/Taxol與敏感細(xì)胞之間內(nèi)源性代謝物的差異,初步探討A2780/Taxol細(xì)胞生物學(xué)特性和耐藥機(jī)制。使用濃度梯度法建立A2780/Taxol細(xì)胞,并通過細(xì)胞形態(tài)觀察,生長曲線測(cè)定,藥物敏感試驗(yàn),細(xì)胞內(nèi)多藥耐藥相關(guān)蛋白(MRP1)、P-糖蛋白(P-gp)和肺耐藥蛋白(LRP)的水平測(cè)定,評(píng)價(jià)A2780/Taxol細(xì)胞的生物學(xué)特性。同時(shí),采用GC-MS的代謝組學(xué)方法分別對(duì)卵巢癌敏感細(xì)胞株與紫杉醇耐藥細(xì)胞株的代謝物指紋圖譜進(jìn)行分析,并通過偏最小二乘法判別分析(PLS-DA)對(duì)代謝組學(xué)數(shù)據(jù)進(jìn)行多元處理。結(jié)果表明:人卵巢癌細(xì)胞敏感細(xì)胞與耐藥細(xì)胞相比,其中琥珀酸、天冬氨酸、果糖、肌醇等13種內(nèi)源性代謝物存在顯著性差異。糖降解、三羧酸(TCA)循環(huán)、肌苷代謝途徑發(fā)生了異常改變,這些差異改變可能與卵巢癌細(xì)胞的耐藥機(jī)制有關(guān)。
[Abstract]:The difference of endogenous metabolites between paclitaxel resistant human ovarian cancer cells A2780/Taxol and sensitive cells was studied by gas chromatography-mass spectrometry (GC-MS), and the biological characteristics and drug resistance mechanism of A2780/Taxol cells were preliminarily investigated. A2780/Taxol cells were established by concentration gradient method. The cell morphology, growth curve, drug sensitivity test and intracellular multidrug resistance-associated protein (MRP1) were determined. The levels of P-glycoprotein (P-gp) and lung resistance protein (LRP) were measured to evaluate the biological characteristics of A2780/Taxol cells. At the same time, the metabolite fingerprints of ovarian cancer sensitive cell line and paclitaxel resistant cell line were analyzed by GC-MS method. Partial least squares discriminant analysis (PLS-DA) was used to process the metabonomics data. The results showed that 13 endogenous metabolites such as succinic acid, aspartic acid, fructose and inositol were significantly different between human ovarian cancer cells and drug-resistant cells. Glucose degradation, tricarboxylic acid (TCA) cycle, and inosine metabolism pathway were abnormal. These differences may be related to the mechanism of drug resistance in ovarian cancer cells.
【作者單位】： 南京工業(yè)大學(xué)藥學(xué)院;
【分類號(hào)】：R737.31;O657.63
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本文編號(hào)：2375179