AKT Inhibitor SC66 Inhibits Proliferation and Induces Apoptosis in Human Glioblastoma Through Down-Regulating AKT/β-Catenin Pathway

Abstract

Glioblastoma multiforme (GBM) is the most common intracranial malignancy in adults with the highest degree of malignancy and mortality. Due to its nature of diffuse invasiveness and high migration, GBM lacks an effective treatment strategy and is associated with poor prognosis. SC66 is a novel AKT inhibitor that has been reported to exert antiproliferative activity in many types of cancer cells. However, it remains unclear whether SC66 has antitumor effects in GBM. In this study, we found SC66 obviously suppressed U87 and U251 cell proliferation and EMT- mediated cell migration and invasion. Moreover, SC66 induced GBM cells apoptosis and arrested cell cycle in G0/G1 phase. Furthermore, SC66 also downregulated AKT signaling pathway in a concentration dependent manner. We also found the level of β-catenin nuclear translocation was prominently downregulated after SC66 treatment. Meanwhile, TCF/LEF luciferase report assay indicated that the activity of TCF/LEF was remarkably suppressed. Elevating β-catenin activity by using IM12 rescued SC66 inhibition‐mediated GBM cell proliferation and metastasis. In addition, SC66 showed significantly suppressed the tumorigenicity compared to the control group in the xenograft mouse model. In conclusion, our study demonstrated that SC66 exerts prominently antitumor efficiency in GBM cells in vivo and in vitro by downregulated AKT/β-catenin pathway.

NPC2 as a Prognostic Biomarker for Glioblastoma Based on Integrated Bioinformatics Analysis and Cytological Experiments

“…In order to verify the function of NPC2 in GBM, we silenced NPC2 in GBM cells. U87-MG and U251 are cell lines often used in the study of GBM ( Gao et al, 2020 ; Tu et al, 2020 ; Xia et al, 2020 ; Zhang G. et al, 2020 ). CCK-8 assay has shown that cell proliferation was inhibited in U87-MG and U251 cells with Sh-NPC2 transfection compared with that in negative control (Sh-NC) ( Figure 6A ).…”

RND1 inhibits epithelial-mesenchymal transition and temozolomide resistance of glioblastoma via AKT/GSK3-β pathway

“… 15 , 16 Results from western blot analysis revealed that the overexpression of RND1 did not affect the protein level of p-MAPK, Smad3 and β-catenin but inhibit the phosphorylation of AKT and GSK3-β. SC66, an inhibitor of AKT phosphorylation, 31 significantly decreased phosphorylated AKT and GSK3-β and reversed the effect of RND1 on EMT-related proteins and cell invasion. It has confirmed that PI3K/Akt signal pathway after activation of EGFR plays an important role in the genesis and development of glioma.…”

CKAP4-mediated activation of FOXM1 via phosphorylation pathways regulates malignant behavior of glioblastoma cells

“…At present, the kinase pathways have been identified as prospective therapeutic targets. A novel AKT inhibitor SC66 exerts prominently antitumor efficiency in vivo and in vitro, contributing to its potential applications for the valid treatment of GBM [54] . Inhibitors with improved pharmacokinetics have been considered for the design and development of anticancer agents to improve the prognosis of GBM.…”