Oksimatrinin, insan glioblastoma üç boyutlu hücre modellerinde invazyonu engelleyici etkisi
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Dosyalar
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Glioblastoma tüm onkolojide tedavisi en zor malignitelerden biridir. Gelişen olanaklara rağmen glioblastoma tedavisinde istenilen sonuçlar gözlenmemektedir. Glioblastoma hücreleri ECM’de invazyonu kolaylaştıracak moleküler değişikliklere neden olur. ECM’in yeniden düzenlenmesinde integrin protein ailesinin etkisi vardır. Trakya Üniversitesi Tıp Fakültesi Tıbbi Biyoloji Anabilim Dalı’nda yetiştirilen U87 üç boyutlu insan glioblastoma hücrelerine belirlenen oksimatrinin etkin dozu uygulandı. MMP’lar beyin ECM bileşenlerini parçalayarak glioblastoma invazyonunda etkilidir. Bizim çalışmamızda oksimatrin MMP9 gen ekspresyonunu anlamlı derecede baskılandı. JAK/STAT sinyalizasyon yolağının hücre membranında bağlanarak başlatan sitokinlerden biri IL6 dır. Klinik çalışmalar IL6 ekspresyonunun düşük sağkalımla ilişkisini göstermiştir. Oksimatrin IL6 ekspresyonunu anlamlı düzeyde artırmasına rağmen STAT3 ekspresyonunda azalmaya ve SOCS3 ekspresyonunda artmaya neden olduğu izlendi. TWIST, SNAIL, SLUG ve ZEB2 gliomalarda EMT’yi indükleyen transkripsiyon faktörlerindendir. Glioblastoma hücrelerinin çoğalması, invazyonu ve angiogenezini artırdıkları gösterilmiştir. Bizim çalışmamızda oksimatrin tarafından SNAIL ve SLUG baskılandı. Çalışma sonucunda Oksimatrinin U87 insan glioblastoma hücrelerinde invazyonu azalttığı tespit edildi.
Glioblastoma is one of the most difficult malignancies to treat in all oncology. Despite the developing possibilities, the desired results are not observed in the treatment of glioblastoma. Glioblastoma cells cause molecular changes in the ECM that facilitate invasion. The integrin family of proteins has an effect on the rearrangement of the ECM. The effective dose of oxymatrine was applied to U87 three-dimensional human glioblastoma cells grown in Trakya University Faculty of Medicine, Department of Medical Biology. MMPs are effective in glioblastoma invasion by degrading brain ECM components. In our study, oxymatrine significantly suppressed MMP9 gene expression. One of the cytokines that initiates the JAK/STAT signaling pathway by binding to the cell membrane is IL6. Clinical studies have shown that IL6 expression is associated with poor survival. Although oxymatrine significantly increased IL6 expression, it was observed that it caused a decrease in STAT3 expression and an increase in SOCS3 expression. TWIST, SNAIL, SLUG, and ZEB2 are transcription factors that induce EMT in gliomas. They have been shown to increase proliferation, invasion and angiogenesis of glioblastoma cells. In our study, SNAIL and SLUG were suppressed by oxymatrine. As a result of the study, it was determined that Oxymatrix reduced invasion in U87 human glioblastoma cells.
Glioblastoma is one of the most difficult malignancies to treat in all oncology. Despite the developing possibilities, the desired results are not observed in the treatment of glioblastoma. Glioblastoma cells cause molecular changes in the ECM that facilitate invasion. The integrin family of proteins has an effect on the rearrangement of the ECM. The effective dose of oxymatrine was applied to U87 three-dimensional human glioblastoma cells grown in Trakya University Faculty of Medicine, Department of Medical Biology. MMPs are effective in glioblastoma invasion by degrading brain ECM components. In our study, oxymatrine significantly suppressed MMP9 gene expression. One of the cytokines that initiates the JAK/STAT signaling pathway by binding to the cell membrane is IL6. Clinical studies have shown that IL6 expression is associated with poor survival. Although oxymatrine significantly increased IL6 expression, it was observed that it caused a decrease in STAT3 expression and an increase in SOCS3 expression. TWIST, SNAIL, SLUG, and ZEB2 are transcription factors that induce EMT in gliomas. They have been shown to increase proliferation, invasion and angiogenesis of glioblastoma cells. In our study, SNAIL and SLUG were suppressed by oxymatrine. As a result of the study, it was determined that Oxymatrix reduced invasion in U87 human glioblastoma cells.
Açıklama
Anahtar Kelimeler
Glioblastoma, İnvazyon, Oksimatrin, Invasion, Oxymatrine
