1.Decursin inhibits EC109 cells proliferation via suppression of JAK2/STAT3 signaling pathway
Changkang KE ; Yuying LIU ; Zhipei ZHANG ; Jiao ZHANG ; Yifang ZHU ; Jinwei LIU ; Ziqian WANG ; Jinbo ZHAO ; Xiaofei LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(4):230-236
Objective To investigate whether decursin(Dec) could inhibit EC109 cells proliferation by suppression of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in human esophageal squamous cell carcinoma.Methods The EC109 cells were treated with Dec(20,40,and 80 pmmol/L) for48 h.The cell viability was evaluated by MTT;the apoptotic cells was labelled by TUNEL;the mitochondrial 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 cells,respectively.After co-application of JAK2 / STAT3 antagonist(AG490),the inhibitory ability of Dec to EC109 was observed from the in vivo and in vitro levels.Results Compared to the control group,different concentrations of Dec dose-dependently 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)%],promoted 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 augment of Caspase-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 mitochondrial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.