GSK-3 beta in DNA repair, apoptosis, and resistance of chemotherapy, radiotherapy of cancer

摘要

Glycogen synthase kinase-3 beta (GSK-3 beta) is an evolutionarily conserved serine/threonine kinase, functioning in numerous cellular processes including cell proliferation, DNA repair, cell cycle, signaling and metabolic pathways. GSK-3 beta is implicated in different diseases including inflammation, neurodegenerative disease, diabetes and cancers. GSK-3 beta is involved in biological processes of tumorigenesis, therefore, it is rational that GSK-3 beta inhibitors were employed to target malignant tumors. The effects of GSK-3 beta inhibitors in combination of radiation and chemotherapeutic drugs have been reported in various types of cancers, suggesting GSK-3 beta would play important roles in cancer treatments. GSK-3 beta is involved in multiple signal pathway including Wnt/beta-catenin, PI3K/PTEN/AKT and Notch. GSK-3 beta also functions in DNA repair through phosphorylation of DNA repair factors and affecting their binding to chromatin. This review focuses on the molecular mechanism of GSK-3 beta in DNA repair, special in base excision repair and double-strands break repair, the roles of GSK-3 beta in inhibition of apoptosis through activation of NF-B kappa, and the effects of GSK-3 beta inhibitors on radio- and chemosensitization of various types of cancers.