Liang Yi-Qiong, Chen Bao-An, Wu Wei-Wei, Gao Feng, Xia Guo-Hua, Shao Ze-Ye, Cheng Jian, Ding Jia-Hua, Gao Chong, Li Guo-Hong, Chen Wen-Ji, Chen Ning-Na, Xu Wen-Lin, Sun Xin-Chen, Liu Li-Jie, Li Xiao-Mao, Wang Xue-Mei
Department of Hematology, Zhongda Hospital, Southeast University Clinical Medical School, Nanjing 210009, Jiangsu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Feb;18(1):67-73.
This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.
本研究旨在探讨藤黄酸（GA）联合四氧化三铁磁性纳米颗粒（Fe3O4-MNP）对白血病的潜在治疗作用。采用MTT法评估U937细胞的增殖及细胞毒性。分别通过显微镜和流式细胞术观察并分析细胞凋亡情况。分别采用定量实时聚合酶链反应和蛋白质印迹法检测基因和蛋白的表达。结果表明，GA对U937细胞的细胞毒性呈剂量和时间依赖性增强。Fe3O4-MNP本身无细胞毒性，但可增强GA对U937细胞增殖的抑制作用。GA与Fe3O4-MNP联合诱导的U937细胞凋亡率高于单独使用GA。观察到GA和Fe3O4-MNP处理后细胞典型的凋亡特征。GA与Fe3O4-MNP联合处理后caspase-3和bax的表达水平高于单独使用GA或Fe3O4-MNP，但bcl-2、NF-κB和survivin的表达下调。结论是Fe3O4-MNP可促进GA诱导的U937细胞凋亡，GA与Fe3O4-MNP联合可能是一种治疗白血病的更安全、毒性更小的新疗法。
