TY - JOUR
T1 - Drug Efficacy Comparison of 3D Forming and Preforming Sphere Models with a Micropillar and Microwell Chip Platform
AU - Doh, Il
AU - Kwon, Yong Jun
AU - Ku, Bosung
AU - Lee, Dong Woo
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C2412); by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (no. 2018R1C1B5045068); and by the X-mind Corps program of the NRF funded by the Ministry of Science, ICT (2018025568).
Publisher Copyright:
© 2019 Society for Laboratory Automation and Screening.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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 IC 50 values of the 17 drugs and found that 7 drugs exhibited a high sensitivity in HCC, which was in agreement with previous studies.
AB - 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 IC 50 values of the 17 drugs and found that 7 drugs exhibited a high sensitivity in HCC, which was in agreement with previous studies.
KW - 3D cell culture
KW - cell encapsulation in alginate
KW - hepatocellular carcinoma (HCC) cell line
KW - high-throughput screening (HTS)
KW - in vitro hepatic tumor model
KW - micropillar/microwell chip
UR - http://www.scopus.com/inward/record.url?scp=85061574962&partnerID=8YFLogxK
U2 - 10.1177/2472555218821292
DO - 10.1177/2472555218821292
M3 - Article
C2 - 30753787
AN - SCOPUS:85061574962
SN - 2472-5552
VL - 24
SP - 476
EP - 483
JO - SLAS Discovery
JF - SLAS Discovery
IS - 4
ER -