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Updated: Jul 27, 2025
A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells
Published on: January 22, 2021
Study on drug screening multicellular model for colorectal cancer constructed by three-dimensional bioprinting
Peipei Wang1, Lejia Sun2, Changcan Li2
1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100730, China.
Abstract:
The existing in vitro models for antitumor drug screening have significant limitations. Many compounds that inhibit two-dimensional (2D) cultured cells do not exhibit the same pharmacological effects in vivo, thereby wasting human and material resources and time during drug development. Therefore, it is crucial to develop new models. Three-dimensional (3D) bioprinting technology has greater advantages in constructing human tissues than sandwich culture and organoid construction. We used 3D bioprinting technology to construct a 3D multicellular model of SW480 cells, tumor-associated macrophages, and endothelial cells. The biological activities of the model were evaluated by immunofluorescence, hematoxylin and eosin staining of frozen pathological sections, and transcriptome sequencing. Compared with 3D bioprinted single-cell model (3D printing-S), 3D bioprinted multicellular models (3D printing-M) showed significantly improved expression of tumor-related genes, including hub genes IL1B, FCGR2A, FCGR3A, CYBB, SPI1, CCL2, ITGAM, and ITGB2. Antitumor drug screening experiment showed that the IC50 values of 5-FU, oxaliplatin, and irinotecan in 3D printing-S group/2D culture group were 31.13 μM/12.79 μM, 26.79 μM/0.80 μM, and 16.73 μM/10.45 μM, respectively. Compared with the 3D printing-S group, 3D printing-M group was significantly more resistant to chemotherapy.
Insights
Three-dimensional (3D) bioprinting creates advanced multicellular tumor models. These 3D models demonstrate increased drug resistance compared to traditional 2D cultures and single-cell 3D models, improving antitumor drug screening accuracy.
Area of Science:
- Biotechnology
- Cancer Research
- Drug Development
Background:
- Traditional two-dimensional (2D) in vitro models for antitumor drug screening have limitations, as many compounds effective in 2D cultures fail to show similar efficacy in vivo.
- This discrepancy leads to wasted resources and time in drug development, highlighting the need for more predictive preclinical models.
Purpose of the Study:
- To develop and evaluate a three-dimensional (3D) multicellular tumor model using 3D bioprinting technology.
- To compare the biological activity and drug response of the 3D multicellular model against single-cell 3D bioprinted models and 2D cultures.
Main Methods:
- Construction of a 3D multicellular model using SW480 cells, tumor-associated macrophages, and endothelial cells via 3D bioprinting.
- Evaluation of the model's biological activities using immunofluorescence, hematoxylin and eosin staining, and transcriptome sequencing.
- Antitumor drug screening using 5-FU, oxaliplatin, and irinotecan to determine IC50 values in different model groups.
Main Results:
- The 3D bioprinted multicellular model (3D printing-M) exhibited significantly enhanced expression of key tumor-related genes compared to the 3D bioprinted single-cell model (3D printing-S).
- Transcriptome sequencing revealed significant differences in gene expression profiles between the multicellular and single-cell 3D models.
- The 3D printing-M group demonstrated significantly higher resistance to chemotherapy drugs (5-FU, oxaliplatin, irinotecan) compared to the 3D printing-S and 2D culture groups.
Conclusions:
- Three-dimensional bioprinting is a superior technology for constructing complex human tissue models compared to sandwich cultures or organoids.
- The developed 3D multicellular tumor model offers a more physiologically relevant platform for preclinical antitumor drug screening.
- This advanced model improves the prediction of drug efficacy and resistance, potentially reducing failures in later stages of drug development.
