Triptolide Suppresses 5-lipoxygenase metabolic pathway and induces apoptosis in pancreatic tumor cell lines
- Author:
- No author available
- Journal Title:
- WORLD CHINESE JOURNAL OF DIGESTOLOGY
- Issue:
- 34
- DOI:
- 10.3969/j.issn.1009-3079.2008.34.004
- Key Word:
- 胰腺癌;雷公藤内酯醇;5-脂氧合酶
Abstract： 目的:探讨雷公藤内酯醇(triptolide,TL)通过抑制5-脂氧合酶(5-lipoxygenase,5-LOX)代谢通路对胰腺癌细胞生长增殖及凋亡的影响.方法:台盼蓝染色检测TL对胰腺癌细胞PANC-1、ASPC-1和SW1990的杀伤作用;流式细胞术分析凋亡率;Real-time PCR和Western blot检测TL对5-LOX表达的影响;ELISA检测5-LOX下游产物LTB4的含量.构建5-LOX表达质粒,筛选稳定转染的Sw1990细胞株(SW1990/5-LoX),western blot检测野生型、转染空质粒、转染5-LOX基因的SW1990细胞5-LOX蛋白表达水平,并检测胰腺癌细胞高表达5-LOX对TL诱导凋亡的影响.结果:TL能诱导胰腺癌细胞凋亡,TL 50 μg/L作用24 h后活细胞比例为PANC-1 70.5%±6.8%,ASPC-1 61.2%±5.6%,SW1990 52.8%±5.3%,比对照组显著减少(P<0.05);凋亡细胞数12 h组与对照组相比,有差异(24.2±3.23vs 9.5±2.18,P<0.05).TL能显著抑制5-LOX表达及LTB4生成.稳定转染后,细胞内5-LOX蛋白表达量是Wt组的4倍左右,培养上清中LTB4表达水平也显著高于Wt组(P<0.01).过表达5-LOX使SW1990细胞增强了对TL诱导凋亡的抵抗作用,细胞死亡和凋亡率均明显低于对照组(P<0.01或0.05).结论:TL可以在体外诱导胰腺癌细胞增殖抑制和细胞凋亡,该效应与TL抑制5-LOX代谢通路的活性可能有直接关系,提示TL可能开发成临床治疗胰腺癌的有效药物.
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