Department of Hematology, The Affiliated Zhongda Hospital, Clinical Medical School, Southeast University, Nanjing, People's Republic of China.
Int J Nanomedicine. 2009;4:251-9. doi: 10.2147/ijn.s7932.
Gambogic acid (GA) has a significant anticancer effect on a wide variety of solid tumors. Recently, many nanoparticles have been introduced as drug-delivery systems to enhance the efficiency of anticancer drug delivery. The aim of this study was to investigate the potential benefit of combination therapy with GA and magnetic nanoparticles of Fe(3)O(4) (MNPs-Fe(3)O(4)). The proliferation of K562 cells and their cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscope and flow cytometry, respectively. Furthermore, real-time polymerase chain reaction and Western blotting analyses were performed to examine gene transcription and protein expression, respectively. The results showed that MNPs-Fe(3)O(4) dramatically enhanced GA-induced cytotoxicity and apoptosis in K562 cells. The typical morphological features of apoptosis treated with GA and MNPs-Fe(3)O(4) were observed under an optical microscope and a fluorescence microscope, respectively. The transcription of caspase-3 and bax gene in the group treated with GA and MNPs-Fe(3)O(4) was higher than that in the GA-alone group or MNPs-Fe(3)O(4)-alone group, but the transcription of bcl-2, nuclear factor-kappaB, and survivin degraded as did the expression of corresponding proteins in K562 cells. Our data suggests a potential clinical application of a combination of GA and MNPs-Fe(3)O(4) in leukemia therapy.
藤黄酸(GA)对多种实体瘤具有显著的抗癌作用。最近,许多纳米粒子被引入作为药物传递系统,以提高抗癌药物传递的效率。本研究旨在探讨 GA 与四氧化三铁磁性纳米粒子(MNPs-Fe(3)O(4))联合治疗的潜在益处。通过 MTT 法评估 K562 细胞的增殖及其细胞毒性。通过显微镜和流式细胞术分别观察和分析细胞凋亡。此外,还进行了实时聚合酶链反应和 Western blot 分析,分别检查基因转录和蛋白质表达。结果表明,MNPs-Fe(3)O(4)显著增强了 GA 诱导的 K562 细胞毒性和细胞凋亡。在光学显微镜和荧光显微镜下分别观察到用 GA 和 MNPs-Fe(3)O(4)处理后细胞凋亡的典型形态特征。用 GA 和 MNPs-Fe(3)O(4)处理的细胞中 caspase-3 和 bax 基因的转录高于 GA 单独处理组或 MNPs-Fe(3)O(4)单独处理组,但 bcl-2、核因子-κB 和 survivin 的转录以及相应蛋白在 K562 细胞中的表达均下降。我们的数据表明,GA 和 MNPs-Fe(3)O(4)联合应用于白血病治疗具有潜在的临床应用价值。