Synergism Between MLK3 And P110β In The Regulation Of Glioblastoma Cell Proliferation

Objective:To investigate the mechanism of MLK3 in glioblastoma and estimate the synergistic effect Between MLK3 and p11Oβ in the regulation of glioblastoma cell proliferationMaterials and methods:To investigate the expression of MLK3 in glioblastoma issues and cells by western bolt.and siRNA of MLK3 is use to demonstrate the function of MLK3.Next,estimate the Influence of PTEN deficieny in synergism between MLK3 and JNK in glioblastoma cell proliferation and showing the synergistic effect on glioblastoma cell proliferation,compared with combination of PI3KP and JNK inhibitors.Results:MLK3 were frequently overexpressed in 64.5%patients with glioblastoma(20 of 31 are positive)and dramatical overexpressed in 8 patients with glioblastoma recurrence and positively correlated with recurrence of glioblastoma recurrence.Moreover,Decreasing MLK3 expression using siRNAs leading to retarded glioblastoma cell migration and invasion,and inceased cell adhesiveness..PTEN.WT,but not PTEN deficieny,show higher synergistic effect Between PI3Kβ and JNK on glioblastoma cell proliferation and Combination of MLK3 inhibitor URMC-099 and PI3Kβ inhibitor AZD6482 showed stronger synergistic effect on U-87 glioblastoma cell proliferation,compared with combination of PI3Kβ and JNK inhibitors.Conclusion:MLK3 is positively associated with glioblastoma recurrence and play a vital role in glioblastoma cell migration and in invasion.Concurrent inhibition of PI3Kβ and MLK3 showing higher synergistic effect Between PI3Kβ and JNK on suppressing glioblastoma cell proliferation MLK3.It provides a reliable basis for further studies on the combination of PI3K and MLK3 to inhibit the migration and invasion on glioblastoma.