@article{article_1018938, title={The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells}, journal={European Journal of Biology}, volume={80}, pages={138–144}, year={2021}, DOI={10.26650/EurJBiol.2021.1018938}, author={Eryilmaz, Işıl Ezgi and Güney Eskiler, Gamze and Çolakoğlu, Ceyda and Egeli, Ünal and Çeçener, Gülşah}, keywords={Cabazitaxel, Castration-resistant Prostate Cancer, AKT, mTOR, miRNAs}, abstract={<p>Objective: Despite advances in treatment approaches, metastatic castration-resistant prostate cancer (mCRPC) remains a clinical challenge to treat. Cabazitaxel (Cab), a third-line chemotherapy option for mCRPC, exhibits limited efficiency due to the activation of different signaling pathways associated with drug resistance. The PI3K/AKT/mTOR activation has led to mCRPC progression, and long-term acquired Cab resistance. However, we aimed to assess the association of apoptotic efficiency of Cab with the PI3K/AKT/mTOR activation in mCRPC cells in the present study. </p> <p>Materials and Methods: Cell viability, cell death, morphological analysis, PI3K/AKT/mTOR pathway activation by PI3K/MAPK dual activation assay, mRNA and miRNA expression analysis and immunofluorescence staining were performed in the Cabtreated PC3 cells. </p> <p>Results: Cab caused a significant reduction in PC3 cell viability and triggered apoptotic death at 1 and 5 nM for 72 h. Cab significantly induced PI3K/AKT/mTOR activation, and increased mRNA and activated protein levels of AKT and mTOR in PC3 cells, despite its increased apoptotic effect. Furthermore, the expressions of miR-205 and miR-579, the PI3K/AKT/mTORtargeted miRNAs, were upregulated after Cab treatment. Our findings have shown that the Cab treatment activated PI3K/ AKT/mTOR pathway is associated with its apoptotic effect in mCRPC cells. </p> <p>Conclusion: Although further studies are required to investigate the molecular mechanisms accompanying the Cab response in detail, the PI3K/AKT/mTOR activation, as an alteration related to the apoptotic effect of the drug, may play a role in Cab resistance in mCRPC cells, suggesting that combined therapy with PI3K/AKT/mTOR inhibitors may improve the Cab therapeutic efficiency. <br /> </p>}, number={2}, publisher={Istanbul University}, organization={Scientific Research Projects Foundation of Bursa Uludag University}