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The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer
Isil Ezgi Eryilmaz1, Gamze Guney Eskiler2, Unal Egeli1
1Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.
Introduction:
: Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.
Aim:
In this study, we investigated the antimetastatic and EMT-regulatory effects of Cbx on hormone-sensitive metastatic PC cells.
Materials And Methods:
The anticancer effects of Cbx were assessed by WST-1 and Annexin V analysis. The antimetastatic effect of Cbx was evaluated by wound healing and quantitative reverse transcription polymerase chain reaction through EMT-mesenchymal-to-epithelial transition (MET) markers as well as EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.
Results:
Our results showed that, in addition to its apoptotic and anti-migratory activities, Cbx exhibited the EMT-repressor effects through the prominent downregulation of matrix metalloproteinase-9 and Snail levels as EMT-promoting factors, and the significant upregulation of the certain miRNAs, including miR-205, miR-524, and miR-124, which play a role in EMT-repressing by targeting regulators of the EMT-associated genes.
Conclusion:
Although further evaluations are needed to improve the findings, we showed that, in addition to its classical taxane function, Cbx has a regulatory effect on EMT-MET cycling in hormone-sensitive metastatic PC.
Insights
Cabazitaxel (Cbx) demonstrates antimetastatic effects in prostate cancer by suppressing epithelial-mesenchymal transition (EMT). This chemotherapy agent downregulates EMT-promoting factors and upregulates specific microRNAs, suggesting a role in controlling cancer metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epithelial-mesenchymal transition (EMT) is a key driver of cancer metastasis, making its regulation a significant target in anticancer therapies.
- The precise role of cabazitaxel (Cbx), a chemotherapeutic for metastatic castration-resistant prostate cancer (PC), in regulating EMT within metastatic PC remains incompletely understood.
Purpose of the Study:
- To investigate the antimetastatic and epithelial-mesenchymal transition (EMT)-regulatory effects of cabazitaxel (Cbx) on hormone-sensitive metastatic prostate cancer (PC) cells.
Main Methods:
- Anticancer effects of Cbx were assessed using WST-1 and Annexin V assays.
- Antimetastatic effects were evaluated via wound healing assays and quantitative reverse transcription polymerase chain reaction (qRT-PCR).
- Analysis focused on EMT-MET markers and EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.
Main Results:
- Cabazitaxel (Cbx) exhibited apoptotic and anti-migratory activities.
- Cbx demonstrated EMT-repressor effects by downregulating matrix metalloproteinase-9 (MMP-9) and Snail, key EMT promoters.
- Significant upregulation of miR-205, miR-524, and miR-124 was observed, which are known to repress EMT by targeting EMT-associated gene regulators.
Conclusions:
- Cabazitaxel (Cbx) possesses EMT-regulatory capabilities beyond its conventional taxane function in hormone-sensitive metastatic prostate cancer (PC).
- Cbx influences the EMT-MET (mesenchymal-to-epithelial transition) cycling, indicating a potential role in controlling metastatic processes.
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