Wang Tingting, Wei Jia, Qian Xiaoping, Ding Yitao, Yu Lixia, Liu Baorui
Department of Oncology, Drum Tower Hospital, Clinical Cancer Institute of Nanjing University, Zhongshan Road 321, Nanjing 210008, China.
Cancer Lett. 2008 Apr 18;262(2):214-22. doi: 10.1016/j.canlet.2007.12.004. Epub 2008 Jan 11.
Chemoresistance is a major obstacle to successful cancer chemotherapy. In this study, we examined the ability of gambogic acid (GA) to reverse docetaxel resistance in BGC-823/Doc gastric cancer cells.
The cytotoxic and apoptotic effect of drugs were evaluated by MTT assay and double staining with both Annexin-V-FITC and PI. Cell cycle analysis was determined by PI-stained flow cytometry. Expression of survivin and bcl-2 were evaluated by real-time quantitative RT-PCR.
Treatment of BGC-823/Doc cells with gambogic acid at concentrations of 0.05 microM, 0.1 microM, and 0.2 microM, led to a dramatic increase in docetaxel-induced cytotoxicity without any cytotoxicity by itself. In parallel, gambogic acid treatment caused an increase in apoptotic cell death by docetaxel. Cell cycle analysis indicated that gambogic acid treatment potentiated docetaxel-induced G2/M arrest. Analysis of apoptotic associated gene revealed that gambogic acid singly or in combination with docetaxel significantly downregulate the mRNA expression of survivin, while with no effect on bcl-2.
Our results describe the potential role of gambogic acid to reverse docetaxel resistance though downregulation of survivin, which may make it an attractive new agent for the chemosensitization of cancer cells.
化疗耐药是癌症化疗成功的主要障碍。在本研究中，我们检测了藤黄酸（GA）逆转BGC-823/Doc胃癌细胞对多西他赛耐药的能力。
通过MTT法以及Annexin-V-FITC和PI双染评估药物的细胞毒性和凋亡作用。采用PI染色的流式细胞术进行细胞周期分析。通过实时定量RT-PCR评估survivin和bcl-2的表达。
用浓度为0.05微摩尔/升、0.1微摩尔/升和0.2微摩尔/升的藤黄酸处理BGC-823/Doc细胞，导致多西他赛诱导的细胞毒性显著增加，而其本身无任何细胞毒性。同时，藤黄酸处理使多西他赛诱导的凋亡细胞死亡增加。细胞周期分析表明，藤黄酸处理增强了多西他赛诱导的G2/M期阻滞。凋亡相关基因分析显示，藤黄酸单独或与多西他赛联合使用均显著下调survivin的mRNA表达，而对bcl-2无影响。
我们的结果表明藤黄酸可能通过下调survivin发挥逆转多西他赛耐药的作用，这可能使其成为一种有吸引力的癌细胞化学增敏新药物。
