A Systematic Comparative Assessment of the Response of Ovarian Cancer Cells to the Chemotherapeutic Cisplatin in 3D Models of Various Structural and Biochemical Configurations—Does One Model Type Fit All?

SIMPLE SUMMARY: Epithelial Ovarian Cancer is considered to be a ‘silent killer’ and a challenge for gynaecological health across the world due to its asymptotic nature in the early stages, its late-stage diagnosis, high recurrence rate and resistance to currently available treatment methods (chemotherapy). These disheartening figures highlight the need for extensive in vitro studies to better understand this disease. A number of in vitro 3D models are currently available to aid in the study of ovarian cancer and its response to therapeutic methods. In this work, we report, for the first time, a comprehensive comparative study of three widely used 3D in vitro models for ovarian cancer, along with chemotherapy assessment of primary and metastatic cells. Our study highlights the importance of selecting an appropriate 3D in vitro platform, which is based on multiple factors including the origin of cells used, experimental time period and experimental design, even for one specific disease. ABSTRACT: Epithelial Ovarian Cancer (EOC) is a silent, deadly and aggressive gynaecological disease with a relatively low survival rate. This has been attributed, to some extent, to EOC’s high recurrence rate and resistance to currently available platinum-based chemotherapeutic treatment methods. Multiple groups have studied and reported the effect of chemotherapeutic agents on various EOC 3D in vitro models. However, there are very few studies wherein a direct comparative study has been carried out between the different in vitro 3D models of EOC and the effect of chemotherapy within them. Herein, we report, for the first time, a direct comprehensive systematic comparative study of three different 3D in vitro platforms, namely (i) spheroids, (ii) synthetic PeptiGels/hydrogels of various chemical configurations and (iii) polymeric scaffolds with coatings of various extracellular matrices (ECMs) on the cell growth and response to the chemotherapeutic (Cisplatin) for ovary-derived (A2780) and metastatic (SK-OV-3) EOC cell lines. We report that all three 3D models are able to support the growth of EOC, but for different time periods (varying from 7 days to 4 weeks). We have also reported that chemoresistance to Cisplatin, in vitro, observed especially for metastatic EOC cells, is platform-dependent, in terms of both the structural and biochemical composition of the model/platform. Our study highlights the importance of selecting an appropriate 3D platform for in vitro tumour model development. We have demonstrated that the selection of the best platform for producing in vitro tumour models depends on the cancer/cell type, the experimental time period and the application for which the model is intended.