Targeting Pro-Survival Autophagy Enhanced GSK-3 β Inhibition-Induced Apoptosis and Retarded Proliferation in Bladder Cancer Cells

Curr Oncol. 2023 May 28;30(6):5350-5365. doi: 10.3390/curroncol30060406.ABSTRACTAdvanced bladder cancer (BC) (local invasive and/or metastatic) is not curable even with cytotoxic chemotherapy, immune checkpoint inhibitors, and targeted treatment. Targeting GSK-3β is a promising novel approach in advanced BC. The induction of autophagy is a mechanism of secondary resistance to various anticancer treatments. Our objectives are to investigate the synergistic effects of GSK-3β in combination with autophagy inhibitors to evade GSK-3β drug resistance. Small molecule GSK-3β inhibitors and GSK-3β knockdown using siRNA promote the expression of autophagy-related proteins. We further investigated that GSK-3β inhibition induced the nucleus translocation of transcription factor EB (TFEB). Compared to the GSK-3β inhibition alone, its combination with chloroquine (an autophagy inhibitor) significantly reduced BC cell growth. These results suggest that targeting autophagy potentiates GSK-3β inhibition-induced apoptosis and retarded proliferation in BC cells.PMID:37366889 | PMC:PMC10297715 | DOI:10.3390/curroncol30060406
Source: Current Oncology - Category: Cancer & Oncology Authors: Source Type: research