Kansere Yeni Yaklasim: Akciger Kanserinde in Vitro Antianjiyogenik Tedavi
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2019
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info:eu-repo/semantics/openAccess
Özet
Amaç: Anjiyogenez, endotelyal hücreler, malign durumlardaki tümör hücrelerinin yanı sıra kemik iliği kaynaklı hücreler ve stromal hücreleri içeren tümör mikroçevresindeki hücreleri kapsayan çok faktörlü ve çok hücreli bir kompleks (pato-)fizyolojik olaydır. Bu olayın ana faktörü, vasküler endotelyal büyüme faktörüdür (VEGFA). Son yillarda tümör hücrelerinde potansiyel damarlanma sinyalini bloke etmek için VEGFA reseptörüne karşı Bevacizumab (anti-VEGF) ajani kullanılmaktadır ve akciğer kanseri (NSCLC), kolorektal kanser, meme kanseri ve renal hücreli karsinomada in vitro deneylerle farklı etkinlikleri belirlenmiştir. Bu çalışmadaki temel hedef, Bevacizumab uygulanmış akciğer kanser hücrelerinde damarlanma etkinliği ve mekanizmasının normal hücrelerle karşılaştırılarak belirlenmesidir. Gereç ve Yöntem: Ana uyarıcı VEGF ve anjiyogenez blokajını sağlayan Bevacizumab uygulamaları ile hücre fonksiyonları incelendi. Normal epithelial HUVEC hattı ile akciğer kanser A549 hücre hattı kullanıldı ve ATCC protokolune göre kültüre edildi. Farklı dozlarda ajanlar uygulandıktan sonra, hücre canlılığı, Sytox çoğalma indeksi ve anjiyogenezden sorumlu basamak Notch etkinliği araştırıldı. Bulgular: VEGF ile muamele edilen hücrelerde 24 saat inkubasyon ile hücre canlılığında belirgin artış saptandı. Iki hücre hattında canlılık düzeyleri karşılaştırıldığında VEGF etkisinin anlamlı derecede farklı olduğu görüldü. Bevacizumab uygulamasında ise, A549 hücrelerinin çoğalma indeksi anlamlı derece azaldı ve Notch mekanizması ile ilişkili ADAM10 protein düzeyinin, HUVEC hücresine göre anlamlı artış gösterdiği tespit edildi. Sonuç: Elde edilen bulgulara göre anjiyogenez moleküler mekanizmasının açıklanması adına daha detaylı çalışmalara ihtiyaç olduğu görülmektedir. Geleneksel kanser tedavi yöntemleri yanı sıra etkisi bilinen antianjiyogenik ajanlarla kombine tedavilerin arttırılması başarı şansını arttıracaktır.
Objective: Angiogenesis is physiological event which involve endothelial cells and in malignant conditions involve bone-marrow derived cells, stromal cells related to tumor microenvironment is a multifactorial event. The main factor in this action is vascular endothelial growth factor (VEGFA). In recent years, bevacizumab (anti-VEGF) agent has been used against VEGFA receptor to block potential vascular signal in tumor cells and different activities were determined by in vitro experiments in lung cancer (NSCLC), colorectal cancer, breast cancer and renal cell carcinoma. The main objective of this study was to determine the vascularity and mechanism of vascular cancer in Bevacizumabtreated lung cancer cells compared to normal cells. Methods: Study of cell functions with main stimulant VEGF and Bevacizumab applications which provide angiogenesis blockade. Normal epithelial HUVEC line and lung cancer A549 cell line were used and cultured according to ATCC protocol. After application of different doses of agents, cell viability, Sytox proliferation index and Notch pathway activity responsible for angiogenesis were investigated. Results: Cells treated with VEGF showed a significant increase in cell viability with incubation for 24 hours. VEGF effect was significantly different in two cell lines compared to viability. In the application of Bevacizumab, the proliferation index of A549 cells decreased significantly and the ADAM10 protein level associated with the Notch mechanism was found to increase significantly compared to HUVEC cell. Conclusion: According to the findings, it is seen that it needs more detailed studies to explain the molecular mechanism of angiogenesis. In addition to conventional cancer treatment methods, enhancing combined therapies with known antiangiogenic agents will increase the chances of success.
Objective: Angiogenesis is physiological event which involve endothelial cells and in malignant conditions involve bone-marrow derived cells, stromal cells related to tumor microenvironment is a multifactorial event. The main factor in this action is vascular endothelial growth factor (VEGFA). In recent years, bevacizumab (anti-VEGF) agent has been used against VEGFA receptor to block potential vascular signal in tumor cells and different activities were determined by in vitro experiments in lung cancer (NSCLC), colorectal cancer, breast cancer and renal cell carcinoma. The main objective of this study was to determine the vascularity and mechanism of vascular cancer in Bevacizumabtreated lung cancer cells compared to normal cells. Methods: Study of cell functions with main stimulant VEGF and Bevacizumab applications which provide angiogenesis blockade. Normal epithelial HUVEC line and lung cancer A549 cell line were used and cultured according to ATCC protocol. After application of different doses of agents, cell viability, Sytox proliferation index and Notch pathway activity responsible for angiogenesis were investigated. Results: Cells treated with VEGF showed a significant increase in cell viability with incubation for 24 hours. VEGF effect was significantly different in two cell lines compared to viability. In the application of Bevacizumab, the proliferation index of A549 cells decreased significantly and the ADAM10 protein level associated with the Notch mechanism was found to increase significantly compared to HUVEC cell. Conclusion: According to the findings, it is seen that it needs more detailed studies to explain the molecular mechanism of angiogenesis. In addition to conventional cancer treatment methods, enhancing combined therapies with known antiangiogenic agents will increase the chances of success.
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