Meklofenamik asit vimentin ifadesini düzenleyerek LNCaP prostat kanseri hücrelerinin invazyon ve migrasyonunu inhibe eder

Amaç: Prostat kanserinde erken teşhise ve yeni tedavi ajanlarının geliştirilmesine yönelik çeşitli çalışmalara rağmen, tedavide önemli bir ilerleme kaydedilememiştir. Ayrıca, prostat kanserinde metastaz tedavide büyük zorluk oluşturmaktadır. Bu nedenle, bu çalışmada nonsteroid antiinflamatuar bir ilaç olan meclofenamik asidin (MA) LNCaP prostat kanseri hücrelerinin migrasyonu ve invazyonu üzerine etkisinin araştırılması amaçlanmıştır. Yöntem: İlk olarak, MA'nın LNCaP hücrelerine toksik olmayan konsantrasyonları, tripan mavisi analizi ile belirlendi. Daha sonra, MA'nın migrasyon ve invazyon üzerindeki etkisi, sırasıyla yara iyileştirme analizi ve matrigel invazyon analizi ile değerlendirildi. Son olarak, epitelyal-mezenkimal hücre geçişi için bir belirteç olan vimentinin ifade düzeyi western blotlama ile tespit edildi. Bulgular: Tripan mavisi analizinin sonuçları, 60 ve 80 µM MA konsantrasyonlarının hücreler için toksik olmadığını göstermiştir. İlaç uygulanmamış kontrol hücrelerinin migrasyon oranı %44,4 iken, bu oran 60 ve 80 µM MA uygulanmış gruplarda istatistiksel olarak önemli ölçüde, sırasıyla, %12,9 ve %2,9'a düşmüştür. 80 µM MA uygulanan hücrelerde invazyon oranının %52'den %30.3'e düştüğü görülmüştür. Western blotlama sonuçları, MA verilen hücrelerde vimentin ifade seviyesinin önemli ölçüde azaldığını göstermiştir. Sonuç: Çalışma sonucunda, MA'nın vimentin ekspresyon seviyesini azaltarak LNCaP prostat kanseri hücrelerinin migrasyonu ve invazyonunu azalttığı ilk kez gösterilmiştir.

Anahtar Kelimeler:

Meklofenamik Asit, prostat kanseri, invazyon, migrasyon, vimentin

Meclofenamic acid inhibits the invasion and migration of LNCaP prostate carcinoma cells by regulating vimentin expression

Objectives: Despite various studies to improve the early detection and development of novel treatment agents, no significant progress has been made in the treatment of prostate cancer. Moreover, the metastasis of prostate carcinoma is a major challenge in treatment modalities. Therefore, in the present study, it was aimed to investigate the effect of meclofenamic acid (MA), a nonsteroidal anti-inflammatory drug, on the migration and invasion of LNCaP prostate carcinoma cells. Methods: Firstly, the non-toxic concentrations of MA on LNCaP cells were determined by trypan blue exclusion assay. After that, the effect of MA on migration and invasion was assessed by wound healing assay and matrigel invasion assay, respectively. Finally, the expression level of vimentin, which is a marker for epithelial-to-mesenchymal cell transition, was assessed by western blotting. Results: The results of trypan blue exclusion assay showed that 60 and 80 µM concentrations of MA were non-toxic to the cells. The migration rate of non-treated control cells was 44.4%, while it was significantly reduced to 12.9% and 2.9% in 60 and 80 µM MA-treated groups, respectively. When the cells were treated with 80 µM MA, the drug significantly reduced the invasion of LNCaP cells from 52% to 30.3%. Western blot results showed that the level of vimentin expression was significantly decreased in MA-treated cells. Conclusion: The study shows for the first time that MA inhibits the invasion and migration of prostate cancer LNCaP cells by decreasing the expression level of vimentin.

Keywords:

Meclofenamic acid, prostate cancer, invasion, migration, vimentin,

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