Meme Kanseri Hücreleriyle Üç Boyutlu Tümör Modellerinin Geliştirilmesi ve Noç Reseptörü İnhibitörünün Uygulanması

Abstract

Tissue cultures as disease models are indispensable research tools in the preclinical studies. Two-dimensional (2D) culture that composed in the monolayer form cannot bear the extracellular interactions of the natural tissue. Therefore, it cannot present realistic solutions in the disease modelling. Because of that, scientist study on creating three-dimensional tumor models with the usage of three-dimensional (3D) matrixes that developed with the tissue engineering approach. Within the scope of this thesis statement, creating a three-dimensional in vitro model for breast cancer which is one of the widely observed and lethal pathology among women and inhibition of notch receptor on this model is targeted. For this, hydrogel-nanofiber composite, alginate-based matrixes are designed, and porosity introduced to the structure by using glucose. MDA-MB-231 cells were cultured on 3D matrixes. Porous surfaces were obtained especially in glucose treated matrixes by scanning electron microscopy images. Cell proliferation is increased in the all cultures cultured in 3D matrixes in comparison to 2D cultures, cell proliferation is identified as the highest in the matrixes containing glucose. While notch inhibition decreased the proliferation in 2D cultures, it did not affect the proliferation of cells in 3D cultures, in a statistically significant way. The matrixes composed of alginate-hyaluronic acid and glucose provided the best cell proliferation. In conclusion, alginate, hyaluronic acid, glucose and gelatin/chondroitin sulphate composite fiber bearing matrixes identified as cell friendly and creating extracellular matrix mimetic systems suitable for drug development and dosing studies.