Prostat Kanseri Kök Hücrelerinde Zoledronik Asit Tedavisinin Hücre Adezyon Moleküllerine Etkisi

Abstract

Prostat kanserinin tanı ve tedavisine yönelik birçok alanda ilerleme sağlanabilmesine rağmen hastalık bazı vakalar için ölümcül olma niteliğini sürdürmektedir. Hastaların ölümden kurtulması için atılan her adım hedefe yaklaşılmasına yardım etse de halen sonuca ulaşmak için araştırılması gereken pek çok konu bulunmaktadır. Kök hücrenin keşfi ile bu hücrelerin insan sağlığı için önemi anlaşılmış ve tedavide nasıl kullanılacağının belirlenmesine yönelik çalışmalar büyük hız kazanmıştır. İlerleyen yıllarda Kanser Kök Hücresi kavramı ortaya çıkmış ve bu hücrelerin, kök hücre özelliklerini taşıyan ancak tümör dokusu içinde metastazı yapan, tedavi sonrası nükse yol açabilen veya tedaviye direnç̧ geliştiren hücreler oldukları belirlenmiştir. Köklülük özelliğine sahip bu hücreler dışında kalan hücre gurubu kanser kök hücresi olmayan hücre gurubudur ve konvansiyonel kanser tedavisine cevap veren kanser hücrelerdir. Kanserin metastaz yapması ve çevre dokuya invazyonunda adezyon moleküllerinin önemi büyüktür. Yapılan çalışmalar özellikle çoklu ilaç direnci ve epitelial mezenşimal geçişte adezyon moleküllerinin büyük önem kazandığını göstermiştir. Bu çalışmanın amacı prostat kanseri kök hücreleri üzerine zoledronik asit uygulaması sonrası, metastaz geliştirme sürecinde önemli rolü olan adezyon molekülleri üzerine etkisinin incelenmesidir. Bu amaçla DU145 insan prostat kanseri hücre hattından akım sitometri cihazı ile CD133/CD44 yüzey belirteçleri kullanılarak izole edilen kanser kök hücreleri üzerine zoledronik asit tedavisi uygulanmıştır. Kanser kök hücresinde oluşan değişiklikler adezyon molekülleri yönü ile araştırılmıştır. Elde edilen sonuçlar zoledronik asit tedavisi sonrası kanser kök hücresi sayısında önemli bir düşüş olduğunu ve bu uygulamanın CD44, ITGB1, CD29, LAMB1, LAMB3, LAMC1, SPP1, TGFB1, TGFB1, TIMP2, ADAMTS1, ITGB5’de önemli değişimlere yol açtığını göstermiştir. Bu çalışmada in-vitro ortamda zoledronik asit uygulamasının kanser kök hücresi adezyon molekülleri üzerine baskılayıcı etki oluşturduğu ve ilerleyen çalışmalarda bu ilacın klinik kullanımda prostat kanseri tedavisinde uygulanabilme olasılığının olduğunu göstermiştir.

Keywords

• Prostat kanseri;
• kanser kök hücresi
• zoledronik asit
• hücre adezyon molekülleri
• tedavi

Effect of Zoledronic Acid Treatment on Cell Adhesion Molecules in Prostate Cancer Stem Cells

Abstract

Although the diagnosis and treatment of prostate cancer has made a progress, the disease remains fatal for some cases. Every step taken to save patients from death helps to approach the goal but there are still many issues that need to be investigated to reach a result. With the discovery of stem cells, the importance of these cells for human health has been understood and studies on how to use them in treatment have gained great momentum. In the following years, the concept of Cancer Stem Cell has emerged. It has been shown that these cells have stem cell characteristics but metastasize within the tumor tissue. They can cause recurrence after treatment or develop resistance to treatment. The other group of cells with rootedness is the non-cancer stem cell group and are cancer cells that respond to conventional cancer treatment. Adhesion molecules are of great importance in the cancer metastasis and invasion into the surrounding tissue. Studies have shown that adhesion molecules has great importance spesifically in multi-drug resistance and epithelial-mesenchymal transition. The aim of this study is to examine the effect of zoledronic acid application on prostate cancer stem cells on adhesion molecules, which have an important role in the metastasis development process. For this purpose, zoledronic acid treatment was applied to cancer stem cells isolated from DU145 human prostate cancer cell line using a flow cytometry device and CD133/CD44 surface markers. Changes in cancer stem cells have been investigated in terms of adhesion molecules. The results showed that there was a significant decrease in the number of cancer stem cells after zoledronic acid treatment and this application led to significant changes in CD44, ITGB1, CD29, LAMB1, LAMB3, LAMC1, SPP1, TGFB1, TGFB1, TIMP2, ADAMTS1, ITGB5. In this study, it has been shown that zoledronic acid administration in-vitro has a suppressive effect on cancer stem cell adhesion molecules and that this drug may be used in the treatment of prostate cancer in clinical use in further studies.

Keywords

• prostate cancer
• cancer stem cell
• zoledronic acid
• cell adhesion molecules
• treatment

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