紫花前胡素通过JAK2／STAT3抑制EC109细胞的机制  

Decursin inhibits EC109 cells proliferation via suppression of JAK2/STAT3 signaling pathway

作　　者：柯昌康[1] 刘毓英 张志培[1] 张娇 朱以芳[1] 刘金炜 王子乾 赵晋波[1] 李小飞[3] Ke Changkang;Liu Yuying;Zhang Zhipei;Zhang Jiao;Zhu Yifang;Liu Jinwei;Wang Ziqian;Zhao Jinbo;Li Xiaofei(Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi ＇ an 710038, Chian;Department of Respiration, Chang＇ an Hospital, Xi ＇ an 710100, Chin;The Fourth Military Medical University, Xi＇ an 710052, Chin)

机构地区：[1]第四军医大学唐都医院胸外科,710038 [2]西安长安医院呼吸科,710100 [3]第四军医大学员,710032

出　　处：《中华胸心血管外科杂志》2018年第4期230-236,共7页Chinese Journal of Thoracic and Cardiovascular Surgery

基　　金：国家自然科学基金（81572252）

摘　　要：目的探讨Janus激酶2／信号转导子和转录激活子3 （janus kinase 2/signal transducer and activator of transcription 3 ,JAK2/STAT3 ）参与紫花前胡素（Deeursin，Dee）抑制食管鳞癌细胞增殖的潜在机制。方法Dec（20、40、80μmmol／L）处理ECl09细胞48h后，MTT法检测细胞活性；TUNEL标染凋亡细胞；荧光法检测线粒体氧化应激水平；免疫印迹法检测JAK2／STAT3通路和凋亡相关蛋白含量。此外，联合应用特异性阻断JAK2／STAT3（AG490）后，从在体和离体水平观察Dec对EC109的抑制能力。结果相对于对照组，不同浓度的Dec显著下调p-JAK2[至（55．89±6．04）％]和p-STAT3[至（45．27±8．65）％]表达，抑制ECl09细胞活性（至0．43±0．078），增加凋亡率[至（35．31±8．41）％]，降低MMP水平[至（37．23±6．89）％]，提高活性氧簇（reactiveoxygenspecies，ROS）含量至（231．81±19．63）％，减弱谷胱甘肽（glutathione，GSH）活性至（46．78±6．91）％，（P〈0．05），且呈“剂量依赖性”；但未对正常食管上皮HET-1A细胞活性产生明显影响（P〉0．05）。同时，Dec下调Bcl2，上调Bax，并增加Caspase-3的裂解（P〈0．05）。离体和在体水平联合应用AG490均增强Dec抗EC109细胞的能力（P〈0．05）。结论Dec通过抑制JAK2／STAT3通路，激活线粒体氧化应激介导的凋亡，从而发挥抗食管鳞癌的作用。Objective To investigate whether decnrsin（Dec） could inhibit EC109 cells proliferation by suppression of janus kinasc 2/sigual transducer and activator of transcription 3 （ JAK2/STAT3 ） signaling pathway in human esophageal squa-mous cell carcinoma. Methods The EC109 ceils were treated with Dec（20, 40, and 80 p, mmol/L） for48 h. The cell viability was evaluated by MTT; the apoptotic cells was labelled by TUNEL ; the mitoehondrial oxidative stress level was detected by fluorescent staining; and western blotting was used to analyze the proteins of JAK2/STAT3 signaling and apoptosis in EC109 ceils, respectively. After co-application of JAK2 / STAT3 antagonist（ AG490）, the inhibitory ability of Dec to EC109 was ob- served from the in vivo and in vitro levels. Results Compared to the control group, different concentrations of Dec dose-de- pendently down-regulated expressions of p-JAK2 [ （55.89±6.04 ）% ] and p-STAT3 [ （45.27±8.65 ）% ], repressed EC109 cell activity （0.43±0. 078 ）, increased apoptotic rate [ （ 35.31±8.41 ） % ], reduced MMP levels [ （37.23± 6.89） % ], pro-moted reactive oxygen species （ROS） [ （ 231.81±19.63 ） % ], decreased glutathione （ GSH ） activity [ （ 46.78±6.91 ） %, P 〈0.05]. However, Dec did not significantly affect the activity of the normal esophageal epithelium HET-1A cells（P 〉 0.05）. Meanwhile, Dec obviously leaded to reduction of Bcl2, increment of Bax, and augraent of Caspasc-3 cleavage （P 〈 0.05 ）. Additionally, the inhibitory effect of Dec on EC109 was specifically intensified after co-application of AG490 in vivo and in vitro levels（P 〈 0.05 ）. Conclusion Dec can fight against human esophageal squamous cell carcinoma in vitro and in vivo via activation of mitochondfial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.

关 键 词：紫花前胡素 食管鳞癌 Janus激酶2/信号转导子和转录激活子3 线粒体氧化应激 凋亡 

分 类 号：R285[医药卫生—中药学]