藤黄酸对人胃癌细胞系BGC-823的抗癌作用及凋亡诱导作用
Anticancer effect and apoptosis induction of gambogic acid in human gastric cancer line BGC-823.
作者信息
Liu Wei, Guo Qing-Long, You Qi-Dong, Zhao Li, Gu Hong-Yan, Yuan Sheng-Tao
机构信息
Department of Physiology, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2005 Jun 28;11(24):3655-9. doi: 10.3748/wjg.v11.i24.3655.
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 was exposed to GA for 24, 48 and 72 h, the IC(50) value were 1.02+/-0.05, 1.41+/-0.20 and 1.14+/-0.19 micromol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by Annexin-V/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 micromol/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.
目的
研究中药藤黄酸（GA）对人胃癌细胞系BGC-823的抗癌作用，并进一步探讨GA诱导细胞凋亡的机制。
方法
用不同剂量和不同时间的GA处理低分化人胃癌细胞系BGC-823，采用MTT法检测抑制率。通过Annexin-V/PI双染流式细胞术检测GA诱导BGC-823细胞凋亡情况。选择T/C（%）检测GA对人胃腺癌BGC-823裸鼠移植瘤的抑制作用。通过Annexin-V/PI双染流式细胞术和DNA片段化检测法观察裸鼠移植瘤的凋亡情况。为进一步确定GA诱导凋亡的分子机制，采用RT-PCR检测bcl-2和bax基因表达的变化。
结果
GA作用后，低分化人胃癌细胞系BGC-823受到显著抑制，呈剂量依赖性。细胞经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 μmol/L。通过Annexin-V/PI双染流式细胞术观察到GA诱导BGC-823细胞凋亡。当细胞用1.2 μmol/L GA作用48和72 h时，BGC-823细胞的凋亡率分别约为12.96%和24.58%。用GA（8 mg/kg）处理裸鼠时，人胃腺癌BGC-823裸鼠移植瘤的T/C（%）为44.3。同时，在人胃腺癌BGC-823裸鼠移植瘤中观察到GA诱导的凋亡。RT-PCR检测发现bax基因表达增加，bc1-2基因表达减少。
结论
证实GA对人胃癌细胞系BGC-823有抑制作用。该作用与诱导BGC-823细胞凋亡有关，其分子机制可能与凋亡调节基因bcl-2表达降低及凋亡调节基因bax表达增加有关。体内实验结果也证实了这一点。
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