Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials

Abstract Background 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 mechanisms in vivo. In the present study, RADA16-I peptide has the r...

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Main Authors: Hong Song, Guo-hui Cai, Jian Liang, Di-shu Ao, Huan Wang, Ze-hong Yang
Format: Article
Language:English
Published: BMC 2020-06-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12951-020-00646-x
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author Hong Song
Guo-hui Cai
Jian Liang
Di-shu Ao
Huan Wang
Ze-hong Yang
author_facet Hong Song
Guo-hui Cai
Jian Liang
Di-shu Ao
Huan Wang
Ze-hong Yang
author_sort Hong Song
collection DOAJ
description Abstract Background 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 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. Results Consequently, 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. Conclusion Based 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.
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spelling doaj.art-92046250eec04b64ab12e88951727d9e2022-12-22T04:03:46ZengBMCJournal of Nanobiotechnology1477-31552020-06-0118111910.1186/s12951-020-00646-xThree-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterialsHong Song0Guo-hui Cai1Jian Liang2Di-shu Ao3Huan Wang4Ze-hong Yang5College of Basic Medicine, Zunyi Medical UniversityCollege of Basic Medicine, Zunyi Medical UniversitySchool of Resources and Environment, ABA Normal UniversityCollege of Basic Medicine, Zunyi Medical UniversityCollege of Basic Medicine, Zunyi Medical UniversityWest China School of Basic Medical Sciences and Forensic Medicine, Sichuan UniversityAbstract Background 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 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. Results Consequently, 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. Conclusion Based 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.http://link.springer.com/article/10.1186/s12951-020-00646-xNanofiberHydrogel3D cell cultureHO-8910PM cellsChemosensitivityCell growth pattern
spellingShingle Hong Song
Guo-hui Cai
Jian Liang
Di-shu Ao
Huan Wang
Ze-hong Yang
Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
Journal of Nanobiotechnology
Nanofiber
Hydrogel
3D cell culture
HO-8910PM cells
Chemosensitivity
Cell growth pattern
title Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
title_full Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
title_fullStr Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
title_full_unstemmed Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
title_short Three-dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer HO-8910PM cells in nanofibrous microenvironments of three hydrogel biomaterials
title_sort three dimensional culture and clinical drug responses of a highly metastatic human ovarian cancer ho 8910pm cells in nanofibrous microenvironments of three hydrogel biomaterials
topic Nanofiber
Hydrogel
3D cell culture
HO-8910PM cells
Chemosensitivity
Cell growth pattern
url http://link.springer.com/article/10.1186/s12951-020-00646-x
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