To establish a typical tumor model of ovarian cancer which may be more representative and reliable than traditional monolayer culture and pellet, agarose was used as cell vehicle to engineering tumor. Selection of agarose is based on its successful application in tissue engineering with both amenable mechanical and biological properties. In this study, ovarian cancer cell line SKOV3 was encapsulated in agarose hydrogel with cell aggregates and two-dimensional culture as controls. In vitro cell proliferation was assessed by MTT and cell viability was examined at time points of 2, 4, and 6 days. The expression of tumor malignancy markers including matrix metalloproteinase 2, matrix metalloproteinase 9, hypoxia-inducible factor-1α, and vascular endothelial growth factor-A was assessed by real-time polymerase chain reaction. The results showed that cells proliferated more rapidly in three-dimensional agarose culture than controls. Furthermore, upregulation of matrix metalloproteinase 9 and matrix metalloproteinase 2 activity and increased expression of vascular endothelial growth factor-A and hypoxia-inducible factor-1α were shown in agarose-engineered tumors. All the evidences demonstrated that agarose may provide a more favorable environment for cancer cell growth, mimicking the in vivo environment for tumor generation. The novel in vitro tumor model may be useful for the further investigation of anticancer therapeutics.
Keywords: Agarose; ovarian cancer; tumor engineering; tumor microenvironment.