摘要
目的探讨青蒿琥酯对吉西他滨化疗胰腺癌的辅助治疗作用并研究其机制。方法 MTT法检测胰腺癌细胞系Capan-2在青蒿琥酯和不同浓度吉西他滨处理下的细胞活力。Westernblot检测吉西他滨和青蒿琥酯对Capan-2细胞FOXO1、Noxa、Bim表达水平,细胞色素C、Smac/DIABLO从线粒体中的释放量及caspase-9、caspase-3活化水平的影响。流式细胞术检测Capan-2细胞的线粒体膜电位和凋亡率。结果青蒿琥酯辅助治疗明显提高吉西他滨对Capan-2细胞的杀伤活性。青蒿琥酯处理能显著促进Capan-2细胞FOXO1的表达,转染FOXO1小干扰RNA(FOXO1 siRNA)后,青蒿琥酯对吉西他滨的辅助治疗效果受到明显抑制。青蒿琥酯联合吉西他滨能显著诱导Capan-2细胞中Noxa和Bim的过表达,线粒体膜电位的降低,细胞色素C、Smac/DIABLO的释放,caspase-9、caspase-3的活化及凋亡的发生。转染FOXO1siRNA后,青蒿琥酯联合吉西他滨对Capan-2细胞的凋亡诱导途径受到显著抑制。结论青蒿琥酯可上调FOXO1的表达,增强吉西他滨对胰腺癌细胞的凋亡诱导活性。
OBJECTIVE To investigate the adjuvant effect and mechanisms of artesunate on gemcitabine-based chemotherapy in pancreatic cancer.METHODS MTT assay was performed to evaluate the effect of artesunate and different concentrations of gemcitabine on changing the cell viability of Capan-2.Western blot analysis was performed to detect the effect of artesunate and gemcitabine on changing the expression of FOXO1,Noxa,Bim,and release of cytochrome C and Smac/DIABLO from mitochondria and activation of caspase-9,caspase-3 in Capan-2 cells.Flow cytometry analysis was performed to detect the mitochondrial membrane potential(Δφ)and apoptosis of Capan-2.RESULTS Adjuvant therapy of artesunate significantly enhanced the killing activity of gemcitabine against pancreatic cancer in vitro.Artesunate significantly promoted the expression of FOXO1 in Capan-2.However,transfection with FOXO1 siRNA obviously suppressed the adjuvant effect of artesunate on gemcitabine.Combination with gemcitabine and artesunate significantly induced the overexpression of Noxa and Bim,release of cytochrome C and Smac/DIABLO,activation of caspase-9 and caspase-3,suppression ofΔφand occurrence of cell apoptosis in Capan-2 cells.On the other hand,transfection with FOXO1 siRNA obviously suppressed the apoptotic pathway induced by the combination treatment with artesunate and gemcitabine in the Capan-2 cells.CONCLUSION Artesunate enhances the activity of gemcitabine on inducing the apoptosis of pancreatic cancer through the upregulation of FOXO1.
作者
毛其芬
王海
陈弘磊
孔凡慧
姜凯
MAO Qifen;WANG Hai;CHEN Honglei;KONG Fanhui;JIANG Kai(Tongde Hospital of Zhejiang Province,Hangzhou 310000,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2019年第8期924-929,共6页
Chinese Journal of Modern Applied Pharmacy
基金
浙江省科技计划项目(2017C37150)
