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Published on: May 17, 2021
Drug Efficacy Comparison of 3D Forming and Preforming Sphere Models with a Micropillar and Microwell Chip Platform
Il Doh1, Yong-Jun Kwon2, Bosung Ku3
11 Center for Medical Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
Abstract:
Hepatocellular carcinoma (HCC), a major histological subtype of liver cancer, is the third most common cause of cancer-related death worldwide. Currently, many curative standard treatments using target-specific chemotherapeutic agents are being developed. However, drug efficacy tests based on the 2D monolayer cell culture model do not effectively screen the best drug candidates because they do not accurately reflect in vivo tumor microenvironments. Thus, to select the best drug candidates or repositioning drugs, we developed new 3D in vitro hepatic tumor models, including 3D forming and preformed sphere models. A micropillar and microwell chip platform was used for the 3D in vitro liver cell-based model for high-throughput screening. We measured the efficacy of 60 drugs and sorted the most efficacious drugs by comparing the drug response of the 2D monolayer model with the 3D forming and preformed sphere models. Among the 60 drugs, 17 drugs (28.3%) showed a significant high efficacy in the 3D preformed sphere model, while 45 drugs (75%) showed an efficacy in the 2D model. We also calculated the IC50 values of the 17 drugs and found that 7 drugs exhibited a high sensitivity in HCC, which was in agreement with previous studies.
Insights
Developing novel 3D liver cancer models improves drug screening accuracy. These advanced models identify more effective hepatocellular carcinoma (HCC) treatments compared to traditional 2D methods, aiding drug discovery.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
- Current 2D cell culture models lack in vivo relevance for drug efficacy testing.
- Accurate preclinical models are crucial for identifying effective hepatocellular carcinoma treatments.
Purpose of the Study:
- To develop and validate advanced 3D in vitro hepatic tumor models.
- To compare drug efficacy screening between 2D and 3D liver cancer models.
- To identify promising drug candidates for hepatocellular carcinoma treatment and drug repositioning.
Main Methods:
- Utilized a micropillar and microwell chip platform for high-throughput screening.
- Developed 3D forming and preformed sphere models of hepatocellular carcinoma.
- Tested the efficacy of 60 chemotherapeutic agents using both 2D and 3D models.
Main Results:
- 3D preformed sphere models identified 17 drugs (28.3%) with high efficacy, versus 45 drugs (75%) in 2D models.
- Calculated IC50 values for 17 high-efficacy drugs.
- Identified 7 drugs highly sensitive to hepatocellular carcinoma, consistent with prior research.
Conclusions:
- 3D hepatic tumor models offer superior accuracy for drug efficacy screening in hepatocellular carcinoma.
- The developed 3D models facilitate the identification of potent chemotherapeutic agents.
- This approach enhances the selection of effective drugs for liver cancer treatment.
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