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

Abstract

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 μmmol/L) for 48 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). 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. Key words: Decursin; Esophageal squamous cell carcinoma; JAK2/STAT3; Mitochondrial oxidative stress; Apoptosis