新型萘醌类衍生物诱导胃癌细胞系NCI-N87凋亡的作用研究

Effect of Novel Naphthoquinone Derivatives on Inducing Apoptosis of Gastric Cancer NCI-N87 Cells

研究新型萘醌类衍生物诱导胃癌细胞系NCI-N87凋亡的作用。利用化学合成的方法合成七种新型萘醌类衍生物;MTT Assay检测七种萘醌类衍生物对NCI-N87细胞毒性及增殖抑制作用;选取#3化合物11-(5,8二甲氧基1,4-萘醌-2硫)11-酸处理肺癌细胞系A549和肝癌细胞系HepG2检测其细胞毒性;用流式细胞仪检测#3化合物对NCI-N87细胞周期及凋亡的影响。用蛋白质免疫印迹实验检测#3化合物处理NCI-N87细胞凋亡相关蛋白。合成的七种萘醌类衍生物中#3化合物对NCI-N87细胞毒性最强,对NCI-N87细胞有明显的增殖抑制作用;p-Akt、Bcl-xl、pro-caspase-3和pro-PARP的蛋白质表达量减少,cleaved-caspase-8、cleaved-caspase-9和cleaved-PARP的蛋白质表达量增加。新型萘醌类衍生物11-(5,8二甲氧基1,4-萘醌-2硫)11-酸通过Akt信号通路激活caspase家族蛋白诱导胃癌细胞系NCI-N87凋亡。

To investigate the effect of novel naphthoquinone derivatives on inducing apoptosis of gastric cancer nci-n87 cells.Seven new naphthoquinone derivatives were synthesized by chemical synthesis.NCI-N87 cells were treated with seven naphthoquinone derivatives. The viability of NCI-N87 cells was detected by MTT assay.A549,HepG2 cells were treated with #3[11-（5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalen-2-ylthio） undecanoic acid].The viability of A549,HepG2 cells was detected by MTT assay.The cell cycle and apoptosis of NCI-N87 cells were determined by flow cytometer.The apoptotic-related protein expression levels were determined by Western blotting.#3 suppressed the proliferation of NCI-N87 cells.The Annexin V-FITC staining results showed that #3 could induce NCI-N87 cells apoptosis.The Western blotting results showed that #3 could significantly down-regulate p-Akt、Bcl-xl、pro-caspase-3 and pro-PARP protein expression while up-regulate cleaved-caspase-8、cleaved-caspase-9 and cleaved-PARP in NCI-N87 cells.These findings suggested that 11-（5,8-dimethoxy-1,4-dioxo-1,4-dihydronaphthalen-2-ylthio） undecanoic acid could induce gastric cancer cell NCI-N87 apoptosis by activating Akt-caspase signaling pathways.