AG490 regulated the invasion and metastasis of gallbladder SGC -996 cells through JAK/STAT3 pathway
10.3760/cma.j.issn.1008-6706.2017.06.003
- VernacularTitle:AG490对 Janus 蛋白酪氨酸激酶与信号转导和转录激活子3调控的胆囊癌 SGC-996细胞株侵袭和转移的影响
- Author:
Hua SHI
;
Jianbo WANG
;
Jundi PAN
;
Bin YE
- Keywords:
Gallbladder neoplasms;
Protein -tyrosine kinases;
Signal transduction;
Neoplasm inva-sion;
Neoplasm metastasis
- From:
Chinese Journal of Primary Medicine and Pharmacy
2017;24(6):808-811
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of AG490 on the invasion and metastasis of gallbladder SGC -996 cells regulated by JAK/STAT3,and discuss the related mechanism.Methods Cell viability treated with different concentrations of AG490(50,100,200μmol/L)was detected by MTT method.The ability of invasion and metastasis of gallbladder cells was evaluated by Transwell membrane count.The SGC -996 cell apoptosis was detected by flow cytometry.The protein expression of JAK/STAT3 pathway was detected by Western blot.Results The viability inhi-bition rates of different concentrations of AG490 for SGC -996 cells were (17.49 ±3.41)%,(38.66 ±4.57)%, (79.15 ±6.29)% respectively,and with the increasing of concentration,cell viability decreased obviously.Compared with the control group[(1.39 ±0.21)%],the differences were statistically significant(t =8.162,14.111,21.401, all P <0.01 ).The transfer ability inhibition rate of different concentrations of AG490 for SGC -996 cell were (23.18 ±4.53)%,(51.75 ±6.46)%,(81.32 ±7.13)% respectively,and with the increasing of concentration of AG490,the inhibition rate of invasion and metastasis enhanced.Compared with the control group [(1.46 ± 0.42)%],the differences were statistically significant(t =8.269,13.455,19.366,all P <0.01).The apoptosis rate for SGC -996 cells of different concentrations of AG490 were (13.34 ±4.33)%,(28.16 ±6.23)%,(53.61 ± 8.74)% respectively,and cell apoptosis increased with the increasing of concentration.Compared with control group [(0.97 ±0.52)%],the differences were statistically significant(t =4.913,7.533,10.414,all P <0.01).Different concentrations of AG490 can reduce expression of ZFX,STAT3 and Smad1 protein of JAK/STAT3 pathway of SGC -996 cells,compared with the control group,the differences were statistically significant(tZFX =2.154,3.041,4.185, tSTAT3 =7.348,14.892,17.774 and tSmad1 =3.474,5.241,7.718,all P <0.05).Conclusion AG490 can inhibit the invasion and metastasis of gallbladder SGC -996 cells,and the effect depends on dosage.Its mechanism may be relat-ed to the reduction of cell apoptosis and the protein expression of JAK/STAT3 pathway.
