Abstract
BackgroundOvarian cancer is a highly aggressive malignant disease in gynecologic cancer. It is an urgent task to develop three-dimensional (3D) cell models in vitro and dissect the cell progression-related drug resistance mechanisms in vivo. In the present study, RADA16-I peptide has the reticulated nanofiber scaffold networks in hydrogel, which is utilized to develop robust 3D cell culture of a high metastatic human ovarian cancer HO-8910PM cell line accompanied with the counterparts of Matrigel and collagen I.ResultsConsequently, HO-8910PM cells were successfully cultivated in three types of hydrogel biomaterials, such as RADA16-I hydrogel, Matrigel, and collagen I, according to 3D cell culture protocols. Designer RADA16-I peptide had well-defined nanofiber networks architecture in hydrogel, which provided nanofiber cell microenvironments analogous to Matrigel and collagen I. 3D-cultured HO-8910PM cells in RADA16-I hydrogel, Matrigel, and collagen I showed viable cell proliferation, proper cell growth, and diverse cell shapes in morphology at the desired time points. For a long 3D cell culture period, HO-8910PM cells showed distinct cell aggregate growth patterns in RADA16-I hydrogel, Matrigel, and collagen I, such as cell aggregates, cell colonies, cell clusters, cell strips, and multicellular tumor spheroids (MCTS). The cell distribution and alignment were described vigorously. Moreover, the molecular expression of integrin β1, E-cadherin and N-cadherin were quantitatively analyzed in 3D-cultured MCTS of HO-8910PM cells by immunohistochemistry and western blotting assays. The chemosensitivity assay for clinical drug responses in 3D context indicated that HO-8910PM cells in three types of hydrogels showed significantly higher chemoresistance to cisplatin and paclitaxel compared to 2D flat cell culture, including IC50 values and inhibition rates.ConclusionBased on these results, RADA16-I hydrogel is a highly competent, high-profile, and proactive nanofiber scaffold to maintain viable cell proliferation and high cell vitality in 3D cell models, which may be particularly utilized to develop useful clinical drug screening platform in vitro.
Highlights
Ovarian cancer is a highly aggressive malignant disease in gynecologic cancer
When cultured in collagen I, cell nuclei location indicated long cell strips or irregular cell alignment in 3D context. These results suggested that HO-8910PM cells formed distinct cell aggregate growth patterns, such as the multicellular tumor sphe‐ roids (MCTS), cell colonies, cell strips, and cell clusters, which represented the biomimetic cell-to-cell adhesion, junction or HO-8910PM cellnanofiber matrix interactions in 3D cell culture
When paclitaxel was used for the chemosensitivity assay in 3D context, the IC50 values of HO-8910PM cells in RADA16-I hydrogel, Matrigel, and collagen I are 1.58, 1.51, and 1.80-fold higher than HO-8910PM cells in 2D cell culture, respectively. These results possibly suggested that 3D HO-8910PM cell cultures in RADA16-I hydrogel, Matrigel and collagen I were useful to characterize clinical drug responses in cell models, which significantly decreased the chemosensitivity of HO-8910PM cells for both cisplatin and paclitaxel
Summary
Ovarian cancer is a highly aggressive malignant disease in gynecologic cancer. It is an urgent task to develop three-dimensional (3D) cell models in vitro and dissect the cell progression-related drug resistance mecha‐ nisms in vivo. RADA16-I peptide has the reticulated nanofiber scaffold networks in hydrogel, which is utilized to develop robust 3D cell culture of a high metastatic human ovarian cancer HO-8910PM cell line accompanied with the counterparts of Matrigel and collagen I. Since their inception one hundred years ago, two-dimensional (2D) cell cultures produced important data in biomedical sciences, but the limitations of 2D cell culture were evident because cells were cultivated as monolayer. It was one exciting cell technology that 3D cell models shed light on the molecular mechanisms underlying cell–cell communication or developed multi-organ microfluidic chip platform and complex 3D cell co-culture strategies [8,9,10], beyond 3D cell cultures, which surely spurred the substantial efforts towards the cell scaffold-based biomimetic 3D cell culture models and encouraged much cross-disciplinary work among biologists, material scientists, tissue engineers and clinical physicians
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