Title:Dehydrocostus Lactone Induces Apoptosis and Cell Cycle Arrest through Regulation
of JAK2/STAT3/PLK1 Signaling Pathway in Human Esophageal Squamous Cell
Carcinoma Cells
Volume: 22
Issue: 9
Author(s): Ganghua Yang, Binwu Sheng, Ruixiang Li, Qinhong Xu, Lei Zhang*Zhengyang Lu*
Affiliation:
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
- Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Keywords:
Dehydrocostus lactone, apoptosis, cell cycle arrest, esophageal squamous cell carcinoma, STAT3, PLK1.
Abstract:
Background: Dehydrocostus lactone (DEH), one of the sesquiterpene lactones, has shown extensive pharmaceutical
activities, including anti-cancer activity. However, its effects on human esophageal squamous cell carcinoma
(ESCC) cells are still unknown.
Objective: To investigate the effect of DEH on ESCC cells and the underling molecular mechanisms.
Methods: The cell proliferation was tested using CCK-8 and colony formation assay. Apoptosis was analyzed by flow
cytometry, hoechst staining and caspase-3 activity assay. Cell cycle was analyzed by flow cytometry. IL-6 (STAT3
activator) was used to activate JAK2/STAT3 pathway. Immunofluorescence assay was performed to detect intracellular
location of STAT3. SiRNA transfection was performed to knock down the expression of PLK1. The protein expression
was analyzed by western blotting assay.
Result: DHE treatment significantly reduced the viability of ESCC cells through apoptosis induction and cell cycle
arrest. Furthermore, DHE treatment significantly inhibited the phosphorylation of JAK2 and STAT3. IF assay showed
that the distribution of STAT3 in the nucleus was decreased by DHE treatment. In addition, coculture with IL-6 significantly
prevented the inhibition of phosphorylation of JAK2 and STAT3 by DHE treatment and partly reversed the
effect of DHE on ESCC cells. Moreover, DHE treatment significantly down-regulated the expression of PLK1, which
was partly reversed by IL-6 coculture. Finally, knock down of PLK1 using siRNA reduced the viability of ESCC cells
and induced apoptosis and cell cycle arrest
Conclusion: Our study demonstrated that DHE has a potent anti-cancer effect on ESCC cells through apoptosis induction
and cell cycle arrest via JAK2/STAT3/PLK signaling pathway.