LDH-A inhibitor as a remedy to potentiate the anticancer effect of docetaxel in prostate cancer
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info:eu-repo/semantics/openAccessAttribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/Date
2024Author
Çakıcı, ÇağrıDaylan, Benay
Ünlüer, Rüveyde Safiye
Emekli Alturfan, Ebru
Ayla, Şule
Eren Gözel, Hilal
Yiğit, Pakize
Yavuz Dokgöz, Elif
Yiğitbaşı, Türkan
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Çakıcı, Ç., Daylan, B., Ünlüer, R. S., Emekli Alturfan, E., Ayla, Ş., Eren Gözel, H. ... Yiğitbaşı, T. (2024). LDH-A inhibitor as a remedy to potentiate the anticancer effect of docetaxel in prostate cancer. Journal of Cancer, 15(3), 590-602. https://dx.doi.org/10.7150/jca.86283Abstract
Increased LDH-A activity promotes tumor growth, migration, invasion, and metastasis. This study aimed to investigate the effects of the combination of LDH-A inhibitor and Docetaxel on apoptosis and epithelial-mesenchymal transition (EMT) in the murine prostate cancer (PCa) model. The prostate cancer murine model was developed subcutaneously in 50 male B57CL/6 mice using the Tramp-C2 prostate cancer cell line. From the tumor tissue samples, apoptosis analysis was performed using TUNEL staining, and EMT was investigated using western blot and qPCR. Hematoxylin-eosin staining (HE) and Periodic acid-Schiff staining were used to histopathologically examine liver and kidney tissues. Lactate levels revealed that the Warburg effect was reversed with the LDH-A inhibitor. Both serum and tumor tissue apoptosis increased, and tumor sizes reduced in PCa+LDH-A inhibitor + Docetaxel treatment groups (p<0.05). The combination of LDH-A inhibitor and Docetaxel inhibited EMT mechanism by causing a decrease in Snail, Slug, Twist, and HIF-1α expressions as well as a decrease in N-cadherin and an increase in E-cadherin levels. Reprogramming glucose metabolism with an LDH-A inhibitor can increase the effectiveness of Docetaxel on apoptosis and metastasis mechanisms in PCa.
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Journal of CancerVolume
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