Drug Efficacy Comparison of 3D Forming and Preforming Sphere Models with a Micropillar and Microwell Chip Platform

Il Doh, Yong Jun Kwon, Bosung Ku, Dong Woo Lee*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)476-483
Number of pages8
JournalSLAS Discovery
Volume24
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019
Externally publishedYes

Keywords

  • 3D cell culture
  • cell encapsulation in alginate
  • hepatocellular carcinoma (HCC) cell line
  • high-throughput screening (HTS)
  • in vitro hepatic tumor model
  • micropillar/microwell chip

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