Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823
Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823
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DOI：
10.3748/wjg.v11.i24.3655
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发表时间：
2005-06-28
影响因子：
4.3
通讯作者：
Yuan, Sheng-Tao
中科院分区：
文献类型：
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作者：
Liu, Wei;Guo, Qing-Long;Yuan, Sheng-Tao
目的：目的：研究中药藤黄酸（GA）对人胃癌BGC-823细胞的抑制作用，并进一步探讨GA诱导细胞凋亡的机制。方法：采用MTT法检测不同剂量GA对低分化人胃癌BGC-823细胞的抑制率，并观察GA诱导细胞凋亡的作用时间。Annexin-V/PI双染流式细胞术检测GA诱导BGC-823细胞凋亡的作用。以T/C（%）为指标检测GA对人胃腺癌BGC-823裸鼠移植瘤的抑制作用。Annexin-V/PI双染流式细胞术和DNA片段化分析法观察裸鼠移植瘤细胞凋亡情况。为进一步探讨GA诱导胃癌细胞凋亡的分子机制，采用RT-PCR方法检测GA对bcl-2和bax基因表达的影响。结果：GA对低分化胃癌细胞株BGC-823有明显的抑制作用，且呈剂量依赖性。GA作用24、48和72 h后，IC_（50）值分别为1.02 ± 0.05、1.41 ± 0.20和1.14 ± 0.19 μ mol/L。AnnexinV/PI双重染色流式细胞仪检测GA诱导BGC-823细胞凋亡。1.2 μ mol/L GA作用于BGC-823细胞48和72 h后，细胞凋亡率分别为12.96%和24.58%。GA（8mg/kg）对人胃癌BGC-823裸鼠移植瘤的T/C（%）为44.3。同时，GA诱导人胃癌BGC-823裸鼠移植瘤细胞凋亡。RT-PCR检测发现Bax基因表达上调，bc 1 - 2基因表达下调。结论：GA对人胃癌细胞BGC-823有抑制作用。该作用与诱导BGC-823细胞凋亡有关，其分子机制可能与降低凋亡调控基因bcl-2的表达，提高凋亡调控基因bax的表达有关。该结果也在体内得到证实。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells were exposed to GA for 24, 48 and 72 h, the IC50 value was 1.02 +/- 0.05, 1.41 +/- 0.20 and 1.14 +/- 0.19 mu mol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by AnnexinV/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 mu mol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.