Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer.

Autor:	Sevim Nalkiran H; Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey., Akcora Yildiz D; Department of Biology, Faculty of Arts and Sciences, Mehmet Akif Ersoy University, Burdur, Turkey., Saydam F; Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey., Guzel AI; Department of Medical Biology, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik, Turkey., Nalkiran I; Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.
Jazyk:	angličtina
Zdroj:	Saudi journal of biological sciences [Saudi J Biol Sci] 2023 Mar; Vol. 30 (3), pp. 103564. Date of Electronic Publication: 2023 Jan 23.
DOI:	10.1016/j.sjbs.2023.103564
Abstrakt:	Improving the chemotherapy sensitivity of bladder cancer is a current clinical challenge. It is critical to seek out effective combination therapies that include low doses of cisplatin due to its dose-limiting toxicity. This study aims to investigate the cytotoxic effects of the combination therapy including proTAME, a small molecule inhibitor, targeting Cdc-20 and to determine the expression levels of several APC/C pathway-related genes that may play a role in the chemotherapy response of RT-4 (bladder cancer) and ARPE-19 (normal epithelial) cells. The IC20 and IC50 values were determined by MTS assay. The expression levels of apoptosis-associated ( Bax and Bcl-2) and APC/C-associated (Cdc-20 , Cyclin-B1 , Securin, and Cdh-1) genes were assessed by qRT-PCR. Cell colonization ability and apoptosis were examined by clonogenic survival experiment and Annexin V/PI staining, respectively. Low-dose combination therapy showed a superior inhibition effect on RT-4 cells by increasing cell death and inhibiting colony formation. Triple-agent combination therapy further increased the percentage of late apoptotic and necrotic cells compared to the doublet-therapy with gemcitabine and cisplatin. ProTAME-containing combination therapies resulted in an elevation in Bax/Bcl-2 ratio in RT-4 cells, while a significant decrease was observed in proTAME-treated ARPE-19 cells. Cdc-20 expression in proTAME combined treatment groups were found to be decreased compared to their control groups. Low-dose triple-agent combination induced cytotoxicity and apoptosis in RT-4 cells effectively. It is essential to evaluate the role of APC/C pathway-associated potential biomarkers as therapeutic targets and define new combination therapy regimens to achieve improved tolerability in bladder cancer patients in the future. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Author(s).)
Databáze:	MEDLINE
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