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

Autor: Shirono, Yuko, Bilim, Vladimir, Anraku, Tsutomu, Kuroki, Hiroo, Kazama, Akira, Murata, Masaki, Hiruma, Kaede, Tomita, Yoshihiko
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Zdroj: Current Oncology; Jun2023, Vol. 30 Issue 6, p5350-5365, 16p, 2 Diagrams, 3 Graphs
Abstrakt: Advanced 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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