小白菊内酯对食管癌细胞增殖 凋亡和能量代谢的影响  

Effects of parthenolide on proliferation, apoptosis and energy metabolism of esophageal cancer cells

作　　者：王晓芬[1] 陈雪芬 戴小燕 Wang Xiaofen;Chen Xuefen;Dai Xiaoyan(Department of Pharmacy,Wenzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University,Wenzhou,Zhejiang 325000,China)

机构地区：[1]浙江中医药大学附属温州市中医院制剂室,浙江温州325000

出　　处：《中国药物与临床》2023年第7期428-435,共8页Chinese Remedies & Clinics

摘　　要：目的 探讨小白菊内酯对食管癌细胞增殖、凋亡和能量代谢的影响。方法 对人食管癌细胞Eca109转染肝激酶B1(LKB1)的短发夹RNA(shRNA)重组pLK0.1质粒(LKB1-shRNA)及阴性对照质粒(NC-shRNA),然后应用不同浓度的小白菊内酯处理Eca109细胞。使用细胞计数试剂(CCK-8)检测试剂盒测量细胞活力。使用Annexin V-异硫氰酸荧光素(FITC)/碘化丙啶(PI)双重染色分析细胞凋亡。使用定量反转录聚合酶链反应(RT-qPCR)和蛋白免疫印迹法检测LKB1、cleaved PARP、磷酸化腺苷酸(AMP)激活蛋白激酶-α(p-AMPK-α)和AMPK-α的蛋白表达。使用Screen Quest荧光法葡萄糖摄取检测试剂盒检测葡萄糖摄取。使用三磷酸腺苷(ATP)分析试剂盒测量细胞ATP水平。结果 与未处理的Eca109细胞相比,10μmol/L小白菊内酯孵育24 h后细胞中LKB1的表达水平升高(P<0.05)。小白菊内酯处理抑制了Eca109细胞的增殖、葡萄糖摄取和ATP合成,并诱导了细胞凋亡(P<0.05)。小白菊内酯处理升高了LKB1、p-AMPK-α和cleaved PARP的蛋白相对表达量(P<0.05)。然而,沉默LKB1则逆转了小白菊内酯对细胞增殖、凋亡、葡萄糖摄取和ATP合成的影响(P<0.05)。结论 小白菊内酯通过激活LKB1-AMPK轴来抑制食管癌细胞增殖、葡萄糖摄取和ATP合成,并诱导细胞凋亡。Objective To reveal the effects of parthenolide on the proliferation,apoptosis and energy metabolism of esophageal cancer cells.Methods Human esophageal cancer cells line Eca109 were transfected with hepatokinase B1(LKB1)short hairpin RNA(shRNA)to recombinant pLK0.1 plasmid(LKB1-shRNA)and negative control plasmid(NC-shRNA),and then Eca109 cells were treated with different concentrations of parthenolide.Cell viability was measured by CCK-8 detection kit.Apoptosis was analyzed by AnnexinV-FITC/pro-pidium iodide(PI)double staining.The protein expressions of LKB1,cleavedPARP,phosphorylated AMPK-αand AMPK-αwere detected by RT-qPCR and Western blotting.Glucose uptake was detected by ScreenQuest fluores-cence glucose uptake detection kit.The level of cellular ATP were measured by ATP analysis kit.Results Com-pared with untreated Eca109 cells,the expression level of LKB1 in the cells was significantly increased after 10μm parthenolide incubation for 24 h(P<0.05).Parthenolide treatment significantly inhibited the proliferation,glucose uptake and ATP synthesis of Eca 109 cells,and induced cell apoptosis(P<0.05).Parthenolide treatment signifi-cantly increased the relative protein expression of LKB1,p-AMPK-αand cleaved PARP(P<0.05).However,si-lencing LKB1 reversed the effects of parthenolide on cell proliferation,apoptosis,glucose uptake and ATP synthe-sis(P<0.05).Conclusion Parthenolide can inhibit the proliferation,glucose uptake and ATP synthesis of esophageal cancer cells,and induce cell apoptosis by activating the LKB1-AMPK axis.

关 键 词：小白菊内酯 LKB1-AMPK轴 食管肿瘤 葡萄糖摄取 ATP合成 细胞凋亡 

分 类 号：R285[医药卫生—中药学]