Abstract 5441: Regulation of AKT phosphorylation by GSK3β and PTEN to control chemoresistance in breast cancer

Abstract

Abstract Background Chemotherapy is an important element in the treatment paradigm for breast cancers. However, the resistance of cancer cells to chemotherapeutic agents frequently results in the subsequent recurrence and metastasis. AKT phosphorylation is highly expressed or over-expressed in chemoresistant tumor samples. However, the precise molecular mechanism involved in AKT phosphorylation-related chemoresistance in breast cancer remains unknown. The aim of the present study was to assess whether the role of AKT phosphorylation in the cell viability and chemoresistance of breast cancer. Methodology/Principal Findings We developed two taxol resisted breast cancer cells: TAX Resis HepG2 and TAX Resis HepG2 SMMC7721. Western blot and immunofluorescence analysis indicated that glycogen synthase kinase 3 beta (GSK3β), phosphorylated phosphatase and tension homologue (p-PTEN) and phosphorylation of AKT (p-AKT) were highly expressed in taxol resisted HepG2 and SMMC7721 cells. The increase of GSK3β phosphorylated and inactivated PTEN, thereby enhanced phosphatidylinositide 3-kinases (PI3K)/Akt signaling. The increase in GSK3β, p-PTEN and p-AKT was associated with cell viability by MTT assay. Annexin-V-PI assay and transwell analysis were indicated that GSK3β knockdown with lentiviral shRNA (shRNA-GSK3β) promoted the apoptosis and suppressed the migration ability of Taxol resisted HepG2 and SMMC7721 cells, and both effects were reversed by activating p-AKT via PTEN inhibitor bpV(pic). Conclusions In conclusion, AKT phosphorylation manipulated by GSK3β and PTEN were correlated with cell viability, migration and apoptosis in Taxol resisted HepG2 and SMMC7721 cells, which may promote chemoresistance of breast cancer. Furthermore, functions of GSK3β can modulate cell viability via the PTEN/PI3K/Akt signaling pathway and induce chemoresistance, serving as a valuable molecular target for treatment of breast cancer. Citation Format: Chunyi Gao, Guohua Wang, Zhenglin Jiang. Regulation of AKT phosphorylation by GSK3β and PTEN to control chemoresistance in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5441.