European Journal of Biology

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DOI :10.26650/EurJBiol.2021.1018938   IUP :10.26650/EurJBiol.2021.1018938    Full Text (PDF)

The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells

Işıl Ezgi Eryılmaz, Gamze Güney Eskiler, Ceyda Çolakoğlu, Ünal Egeli, Gülşah Çeçener

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. 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. 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/mTOR targeted 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. 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.

Keywords: Cabazitaxel, Castration-resistant Prostate Cancer, AKT, mTOR, miRNAs

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APA

Eryılmaz, I.E., Güney Eskiler, G., Çolakoğlu, C., Egeli, Ü., & Çeçener, G. (2021). The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells. European Journal of Biology, 80(2), 138-144. https://doi.org/10.26650/EurJBiol.2021.1018938


AMA

Eryılmaz I E, Güney Eskiler G, Çolakoğlu C, Egeli Ü, Çeçener G. The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells. European Journal of Biology. 2021;80(2):138-144. https://doi.org/10.26650/EurJBiol.2021.1018938


ABNT

Eryılmaz, I.E.; Güney Eskiler, G.; Çolakoğlu, C.; Egeli, Ü.; Çeçener, G. The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells. European Journal of Biology, [Publisher Location], v. 80, n. 2, p. 138-144, 2021.


Chicago: Author-Date Style

Eryılmaz, Işıl Ezgi, and Gamze Güney Eskiler and Ceyda Çolakoğlu and Ünal Egeli and Gülşah Çeçener. 2021. “The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells.” European Journal of Biology 80, no. 2: 138-144. https://doi.org/10.26650/EurJBiol.2021.1018938


Chicago: Humanities Style

Eryılmaz, Işıl Ezgi, and Gamze Güney Eskiler and Ceyda Çolakoğlu and Ünal Egeli and Gülşah Çeçener. “The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells.” European Journal of Biology 80, no. 2 (Jun. 2025): 138-144. https://doi.org/10.26650/EurJBiol.2021.1018938


Harvard: Australian Style

Eryılmaz, IE & Güney Eskiler, G & Çolakoğlu, C & Egeli, Ü & Çeçener, G 2021, 'The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells', European Journal of Biology, vol. 80, no. 2, pp. 138-144, viewed 6 Jun. 2025, https://doi.org/10.26650/EurJBiol.2021.1018938


Harvard: Author-Date Style

Eryılmaz, I.E. and Güney Eskiler, G. and Çolakoğlu, C. and Egeli, Ü. and Çeçener, G. (2021) ‘The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells’, European Journal of Biology, 80(2), pp. 138-144. https://doi.org/10.26650/EurJBiol.2021.1018938 (6 Jun. 2025).


MLA

Eryılmaz, Işıl Ezgi, and Gamze Güney Eskiler and Ceyda Çolakoğlu and Ünal Egeli and Gülşah Çeçener. “The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells.” European Journal of Biology, vol. 80, no. 2, 2021, pp. 138-144. [Database Container], https://doi.org/10.26650/EurJBiol.2021.1018938


Vancouver

Eryılmaz IE, Güney Eskiler G, Çolakoğlu C, Egeli Ü, Çeçener G. The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells. European Journal of Biology [Internet]. 6 Jun. 2025 [cited 6 Jun. 2025];80(2):138-144. Available from: https://doi.org/10.26650/EurJBiol.2021.1018938 doi: 10.26650/EurJBiol.2021.1018938


ISNAD

Eryılmaz, IşılEzgi - Güney Eskiler, Gamze - Çolakoğlu, Ceyda - Egeli, Ünal - Çeçener, Gülşah. “The Activation of PI3K/AKT/mTOR Signaling Pathway in Response to Cabazitaxel Treatment in Metastatic Castration-Resistant Prostate Cancer Cells”. European Journal of Biology 80/2 (Jun. 2025): 138-144. https://doi.org/10.26650/EurJBiol.2021.1018938



TIMELINE


Submitted04.11.2021
Accepted22.11.2021
Published Online07.12.2021

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