Three-dimensional core-shell alginate microsphere for cancer hypoxia simulation in vitro

Yejiao Ruan; Lingyun He; Jiamin Chen; Jinfeng Wang; Shujing Zhao; Xiaoling Guo; Yao Xie; Zhenzhai Cai; Xian Shen; Chao Li

doi:10.3389/fbioe.2023.1174206

Three-dimensional core-shell alginate microsphere for cancer hypoxia simulation in vitro

Front Bioeng Biotechnol. 2023 Apr 11:11:1174206. doi: 10.3389/fbioe.2023.1174206. eCollection 2023.

Authors

Affiliations

¹ The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
² Beijing Automation Control Equipment Institute, Beijing, China.
³ The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

Abstract

Hypoxia is one of the major causes of cancer resistance and metastasis. Currently, it is still lack of convenient ways to simulate the in vivo hypoxic tumor microenvironment (TME) under normoxia in vitro. In this study, based on multi-polymerized alginate, we established a three-dimensional culture system with a core-shell structure (3d-ACS), which prevents oxygen diffusion to a certain extent, thereby simulating the hypoxic TME in vivo. The cell activity, hypoxia inducible factor (HIF) expression, drug resistance, and the related gene and protein changes of the gastric cancer (GC) cells were investigated in vitro and in vivo. The results demonstrated that the GC cells formed organoid-like structures in the 3d-ACS and manifested more aggressive growth and decreased drug responses. Our study provides an accessible hypoxia platform in the laboratory with moderate configuration and it may be applied in studies of the hypoxia-induced drug resistances and other preclinical fields.

Keywords: alginate; hypoxia; hypoxia inducible factor (HIF); three-dimensional culture; tumor microenvironment (TME).

Grants and funding

This work was supported by the 2019 National Undergraduate Innovation and Entrepreneurship Training Program (No. 201910343017), the National Natural Scientific Foundation of China (Nos 81771636, 61903045), Zhejiang Administration of Traditional Chinese Medicine (No. 2017ZB067), the Major scientific technological project of medical and health in Zhejiang Province (No. WKJ-ZJ-1806), the Major Project of Wenzhou Science and Technology Bureau (No. 2018ZY004), and the Public Welfare Research Project of Science Technology Department of Zhejiang Province (No. LGF20H160019).