基于气相色谱-质谱的代谢组学技术研究紫杉醇诱导的卵巢癌A2780耐药株的生物标志物
发布时间：2018-12-12 20:10
【摘要】：采用气相色谱-质谱(GC-MS)的代谢组学技术研究人卵巢癌紫杉醇耐药细胞A2780/Taxol与敏感细胞之间内源性代谢物的差异,初步探讨A2780/Taxol细胞生物学特性和耐药机制。使用浓度梯度法建立A2780/Taxol细胞,并通过细胞形态观察,生长曲线测定,药物敏感试验,细胞内多药耐药相关蛋白(MRP1)、P-糖蛋白(P-gp)和肺耐药蛋白(LRP)的水平测定,评价A2780/Taxol细胞的生物学特性。同时,采用GC-MS的代谢组学方法分别对卵巢癌敏感细胞株与紫杉醇耐药细胞株的代谢物指纹图谱进行分析,并通过偏最小二乘法判别分析(PLS-DA)对代谢组学数据进行多元处理。结果表明:人卵巢癌细胞敏感细胞与耐药细胞相比,其中琥珀酸、天冬氨酸、果糖、肌醇等13种内源性代谢物存在显著性差异。糖降解、三羧酸(TCA)循环、肌苷代谢途径发生了异常改变,这些差异改变可能与卵巢癌细胞的耐药机制有关。
[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.
【作者单位】： 南京工业大学药学院;
【分类号】：R737.31;O657.63
，
本文编号：2375179
[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.
【作者单位】： 南京工业大学药学院;
【分类号】：R737.31;O657.63
，
本文编号：2375179
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