【摘要】 目的探讨姜黄素对耐吉非替尼人肺腺癌PC9/ZD细胞的生物学特性影响以及干预其上皮间质化过程(Epithelial-Mesenchymal Transition,EMT)的相关机制。方法采用体外姜黄素作用于耐吉非替尼人肺腺癌PC9/ZD细胞;分别通过形态学、MTT法、transwell实验检测经姜黄素干预的耐药细胞株的形态特征、药物敏感性和侵袭转移能力的变化;通过Western blot实验检测波形蛋白、上皮钙粘附分子在药物作用后的表达差异以及PI3K/AKT/m TOR信号通路中相关蛋白AKT、m TOR的变化情况。结果与人肺腺癌PC9细胞比较,PC9/ZD耐药细胞株呈间质样细胞表型;与亲代PC9/ZD细胞比较,经姜黄素作用后的PC9/ZD细胞对吉非替尼敏感性明显增强,转移能力减弱(75.67±8.82 vs 103.67±13.67);侵袭能力减弱(17.22±3.63 vs 59.89±8.19);波形蛋白表达下调(1.07±0.23 vs 1.28±0.28),上皮钙粘附分子表达上调(0.82±0.27 vs 0.29±0.11);AKT、m TOR磷酸化减弱(0.20±0.05 vs 0.63±0.17,0.72±0.25 vs 1.10±0.19)。结论姜黄素可以通过阻断PI3K/AKT/m TOR信号通路而明显干预耐吉非替尼肺腺癌细胞上皮-间质转化过程。更多还原

【Abstract】 Objective To explore the effects of curcumin on the biological characteristics and the mechanism of Transition Epithelial-Mesenchymal(EMT) of gefitinib-resistant human lung adenocarcinoma PC9/ZD cell line. Methods PC9/ZD cell line was cultured in vitro with curcumin. Morphological examination, MTT and transwell were performed to detect the morphological characteristics, the drug sensitivity and ability of the invasion and metastasis of drug resistant cell line which were treated with curcumin respectively. By Western blot assay, changs of expressions of vimentin, Ecadherin, AKT and m TOR were tested. Results Compared with human lung adenocarcinoma PC9 cell line, PC9/ZD cell line showed a mesenchymal like phenotype; Compared with the parental PC9/ZD cells, the sensitivity to gefitinib of PC9/ZD cells treated with curcumin was increased; the ability of metastasis and invasion was decreased(75.67±8.82 vs103.67±13.67, 17.22±3.63 vs 59.89±8.19); expression of vimentin was decreased(1.07±0.23 vs 1.28±0.28)and expression of E-cadherin was increased(0.82±0.27 vs 0.29±0.11); phosphorylations of AKT and m TOR were decreased(0.20 ±0.05 vs 0.63±0.17, 0.72±0.25 vs 1.10±0.19). Conclusion Curcumin could intervene the process of epithelial mesenchymal transition of gefitinib-resistant human lung adenocarcinoma cell line by blocking the PI3K/AKT/m TOR signaling pathway.更多还原