Abiraterone and Docetaxel Treatments Increase Phospho-PTEN Expression in Metastatic Prostate Cancer Cells

Abstract

Aim: Prostate cancer is the second leading cause of death in cancer-related deaths in men. Docetaxel and abiraterone acetate are widely used in the treatment of castration-resistant metastatic prostate cancer. Phospho-PTEN triggers proliferation, migration, angiogenesis and survival in cells by causing oncogenic Akt hyperactivation. This study, it is aimed to investigate the effects of docetaxel and abiraterone acetate agents, which are widely used in the treatment of prostate cancer, on the expression of phospho-PTEN, which stimulates the oncogenic pathway.

Material and Methods: The effects of docetaxel and abiraterone acetate on phospho-PTEN expression in androgen receptor (+) and androgen receptor (-) metastatic prostate cancer cell lines were investigated in vitro by immunofluorescence method.

Results: Findings were compatible in both androgen receptor (+) and androgen receptor (-) metastatic prostate cancer cell lines. No statistically significant difference in phospho-PTEN expression was observed between the control and abiraterone acetate groups. Phospho-PTEN expression was increased statistically significant in docetaxel and abiraterone acetate+docetaxel groups compared to control. This increase was greater statistically significant in the combined group given the two agents compared to the docetaxel group.

Conclusion: A significant increase in phospho-PTEN was observed in the docetaxel and combined treatment groups. The increase of Phospho-PTEN causes oncogenic Akt hyperactivation. According to this information, docetaxel and combined drug treatments may support the oncogenic pathway in cells by increasing phospho-PTEN in patients. To eliminate these effects in patients, the administration of agents that dephosphorylate PTEN or agents that will stimulate the pathways that provide dephosphorylation may increase the total survival of the patients.

Keywords

• Prostate
• Cancer
• Phospho-PTEN
• Docetaxel
• Abiraterone

Abirateron ve Docetaxel Tedavileri Metastatik Prostat Kanseri Hücrelerinde Phospho-PTEN Ekspresyonunu Arttırır

Abstract

Amaç: Prostat kanseri erkeklerde kanser ile ilişkili ölümlerde ikinci sırada yer almaktadır. Kastrasyona dirençli metastatik prostat kanseri tedavilerinde dosetaksel ve abirateron asetat yaygın olarak kullanılmaktadır. Phospho-PTEN, onkojenik Akt hiperaktivasyonuna sebep olarak hücrelerde proliferasyon, migrasyon, angiyogenez ve hayatta kalmayı tetikler. Bu çalışmada prostat kanseri tedavisinde yaygın olarak kullanılan dosetaksel ve abirateron asetat ajanlarının onkogenic yolağı uyaran phospho-PTEN ekspresyonu üzerine etkisinin araştırılması amaçlanmışır.

Gereç ve Yöntemler: In vitro olarak antijen reseptör (+) ve androjen reseptör (-) metastatik prostat kanseri hücre hatlarında dosetaksel ve abirateron acetat’ın phospho-PTEN expresyonu üzerine etkisi immünofloresan yöntemi ile araştırılmıştır.

Bulgular: Antijen reseptör (+) ve androjen reseptör (-) metastatik prostat kanseri hücre hatlarının her ikisinde de bulgular birbiriyle uyumluydu. Kontrol ve abirateron asetat grupları arasında phospho-PTEN ekspresyonununda istatistiksel olarak anlamlı bir fark gözlenmedi. Dosetaksel ve abirateron asetat+dosetaksel gruplarında phospho-PTEN ekspresyonu kontrole göre istatistiksel olarak anlamlı şekilde arttı. Bu artış iki ajanın birlikte verildiği kombine grupta dosetaksel grubuna kıyasla istatistiksel olarak anlamlı şekilde daha fazlaydı.

Sonuç: Dosetaksel ve kombine tedavi gruplarında belirgin şekilde phospho-PTEN artışı gözlendi. Phospho-PTEN’in artışı onkojenik Akt hiperaktivasyonuna neden olmaktadır. Bu bilgilere göre, dosetaksel ve kombine ilaç tedavileri hastalarda phospho-PTEN artışına sebep olarak hücrelerde onkojenik yolağı destekliyor olabilir. Hastalarda bu etkilerinin bertaraf edilebilmesi için PTEN’i defosforile edici ajanlar ya da defosforilasyonu sağlayan yolakların uyarılmasını sağlayacak ajanların verilmesi hastaların toplam hayatta kalma sürelerini artırabilir.

Keywords

• Prostat
• Kanser
• Phospho-PTEN
• Docetaxel
• Abirateron

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