Effect of AG490 on JAK2/STAT3 signaling pathway in human retinoblastoma HXO-RB44 cell lines.
10.11817/j.issn.1672-7347.2018.10.004
- Author:
Bei XU
1
;
Xiang CHEN
2
;
Jia TAN
1
;
Xueliang XU
1
Author Information
1. Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, China.
2. Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Cell Survival;
drug effects;
Enzyme Inhibitors;
pharmacology;
Gene Expression Regulation, Neoplastic;
drug effects;
Humans;
Janus Kinase 2;
genetics;
metabolism;
Retinoblastoma;
STAT3 Transcription Factor;
genetics;
metabolism;
Signal Transduction;
drug effects;
Tyrphostins;
pharmacology;
Vascular Endothelial Growth Factor A;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2018;43(10):1061-1067
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the role of Janus kinase (JAK) inhibitor AG490 in the anti-proliferation and cell cycle in human retinoblastoma HXO-RB44 cell lines in vitro, and to explore its effect on the expression of JAK2/signal transducer and activator of transcription 3 (STAT3).
Methods: Cells were divided into an experiment group and a control group, and the experiment group was further divided into 6 sub-groups according to different AG490 concentrations (6.25, 12.50, 25.00, 50.00 or 100.00 μmol/L). Cell proliferation in the different groups was analyzed by cell vitality determination. Cell cycle distribution and apoptosis rate were examined by flow cytometry. The protein levels of STAT3, p-STAT3 and vascular endothelial growth factor (VEGF) were detected by Western blot.
Results: After 48 h treatment with AG490, the viability of HXO-RB44 cells was reduced in a concentration-dependent manner. Compared with the control group, there was no significant difference in the experiment groups except the 6.25 μmol/L group (all P>0.05). The apoptosis rates in the experiment groups were significantly increased with increase in concentration of AG490 compared with that in the control group (all P<0.05). The cell ratio in the G1 phase in 50 or 100 μmol/L group was increased, whereas the cell ratio in the S phase was decreased. Western blot results showed that the expressions of STAT3 and p-STAT3 in the experiment groups were dramatically reduced with the increase in concentration of AG490 compared with that in the control group (all P<0.05). VEGF expression didn't obviously change in the experiment groups with AG490 concentration less than 12.5 μmol/L compared with that in the control group (both P>0.05), but there were significant differences in the other experiment groups (all P<0.05).
Conclusion: JAK inhibitor AG490 can inhibit proliferation and promote apoptosis of the retinoblastoma HXO-RB44 cells through down-regulation of JAK2/STAT3 signaling pathway.
