Effects of Alginate-Gelatin Ratio and Lithium on SK- Hep1 Cell Proliferation Encapsulated in Bio-Polymeric Microspheres

In comparison to 2D systems, 3D tumor culture systems are superior models to mimic the tumor behavior as in vivo. In order to understand the behavior of cells in vitro as they are in vivo, researchers are focusing on 3D systems and these systems are becoming popular as one of the hot techniques for cancer research. One of the aims of this study is to evaluate the effect of natural polymers alginate and gelatin and their ratios on liver adenocarcinoma cells SK-HEP1 spheroids. The second aim is to analyze the effect of lithium on SK-HEP1 spheroids size and number in various ratios of alginate and gelatin. In this study, different concentrations of alginate and gelatin hydrogels were used with SK-HEP1 adenocarcinoma cell line to form multicellular tumor spheroids via the simple droplet-based method. Morphology and size of spheroids which indicates cell proliferation were evaluated using phase-contrast microscopy. Results revealed that gelatin increases cell proliferation without disturbing the morphology of beads up to 1.5% alginate and 0.5% gelatin ratios. Although gelatin supported cell proliferation and growth, over 0.5% of gelatin in biopolymer blend disturbed the bio polymeric bead morphology. Lithium inhibited cell proliferation and decreased the size of cell spheroids. These results are in agreement with the effects of lithium on conventionally cultured SK-HEP1 cells in 2D systems. Our results indicated that cheap and abundant natural polymers such as alginate and gelatin could be potential candidates to create 3D culturing environments including microspheres for cancer.