Zhao Ji’an, Mu Xiu’e, Dong Liang, et al. Inhibitory effects of AG490 on transplanted tumor of nude mice with live cancer through JAK2/STAT3 signal pathway and its mechanism. [J]. Journal of Chongqing Medical University 41(6):580-586(2016)
Zhao Ji’an, Mu Xiu’e, Dong Liang, et al. Inhibitory effects of AG490 on transplanted tumor of nude mice with live cancer through JAK2/STAT3 signal pathway and its mechanism. [J]. Journal of Chongqing Medical University 41(6):580-586(2016) DOI: 10.13406/j.cnki.cyxb.000940.
Inhibitory effects of AG490 on transplanted tumor of nude mice with live cancer through JAK2/STAT3 signal pathway and its mechanism
Objective:To explore the effect of JAK/STAT signal pathway inhibitor AG490 on growth and apoptosis of transplanted tumor of nude mice with human liver cancer and its relationship with the expression of related genes. Methods:The models of transplanted tumor of nude mice with human liver cancer were established. The model mice were randomly divided into 3 groups :control group(normal saline)
low concentration AG490 group(4 mg/kg AG490)
high concentration AG490 group(8 mg/kg AG490)
then saline or AG490 was used to treat the nude mice with the requirements. The growth situations of transplanted tumor in different groups were observed during the treatment
including the body weight
the tumor weight and volume and the inhibiting rates of growth of transplanted tumor. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Western blot was used to detect the expression levels of p-JAK2
JAK2
p-STAT3
STAT3
MMP-2
Bcl-2
Bcl-xl and Bax. The expressions of p-JAK2 and p-STAT3 were observed by immunohistochemistry. Results:Significant differences in tumor weight
volumes
and tumor growth inhibition rates were found between the treatment groups and the control group(P<0.05). Flow cytometric analysis demonstrated the G0/G1 phase in cell cycle was increased in low concentration AG490 group(73.98±0.90)% and high concentration AG490 group(81.39±1.66)% than in control group(59.30±1.13)%
so did cell apoptosis rate of low concentration AG490 group(33.32 ±1.16)% and high concentration AG490 group(52.22 ±1.06)% between control group(1.50 ±0.12)%. Western blot demonstrated both low concentration AG490group(1.073±0.028)(0.955±0.025)and high concentration AG490 group(0.763±0.023)(0.751±0.037)had lower level of pJAK2 and p-STAT3 than control group(1.265±0.012)(1.477±0.020). It shown that the expression of MMP-2
Bcl-2 and Bcl-xl were down-regulated while the expression of Bax was up-regulated after being treated with AG490. Compared with those of control group
the expressions of p-JAK2 and p-STAT3 in AG490 group were decreased by immunohistochemistry(P<0.05). Conclusion:AG490 could promote apoptosis and inhibit the cell growth and invasion by blocking JAK/STAT signal pathway
thereby inhibiting the growth of transplanted tumor of nude mice. The results suggest that the expression of JAK2/STAT3 signal pathway may play an important role in the evolution of liver cancer.
关键词
JAK2/STAT3信号通路AG490肝癌裸鼠移植瘤
Keywords
JAK2/STAT3 signal pathwayAG490Transplanted tumor of nude mice with live cancer