Version 1
: Received: 1 October 2024 / Approved: 1 October 2024 / Online: 1 October 2024 (17:01:31 CEST)
How to cite:
Hiruma, K. Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP. Preprints2024, 2024100084. https://doi.org/10.20944/preprints202410.0084.v1
Hiruma, K. Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP. Preprints 2024, 2024100084. https://doi.org/10.20944/preprints202410.0084.v1
Hiruma, K. Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP. Preprints2024, 2024100084. https://doi.org/10.20944/preprints202410.0084.v1
APA Style
Hiruma, K. (2024). Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP. Preprints. https://doi.org/10.20944/preprints202410.0084.v1
Chicago/Turabian Style
Hiruma, K. 2024 "Acidic Microenvironment Enhances Cisplatin Resistance in Bladder Cancer via Bcl-2 and XIAP" Preprints. https://doi.org/10.20944/preprints202410.0084.v1
Abstract
Cisplatin (CDDP) remains a key drug for patients with advanced bladder cancer (BC), despite the emergence of new therapeutic agents. Identifying factors contributing to treatment resistance to CDDP is crucial. The acidity of the tumor microenvironment has been reported to be associated with treatment resistance and poor prognosis across various cancer types. Our objective was to investigate the effects of an acidic environment on BC cells and elucidate the mechanisms behind CDDP resistance. Our findings show that BC cells cultured in acidic conditions developed resistance to cisplatin as acidity increased. Notably, CDDP administered to BC cells in a pH 6.0 environment required twice the concentration compared to pH 7.5 to achieve equivalent toxicity. Using chloroquine and navitoclax, we identified the involvement of Bcl-2 and LC3B pathways in the acquisition of CDDP resistance under acidic conditions. Western blot analysis revealed that the activation of Bcl-2 and XIAP expression appears to inhibit both apoptotic and autophagic cell death. These results suggest that alleviating the acidity of the tumor microenvironment in clinical settings might enhance BC sensitivity to CDDP.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
