Selective colony area method for heterogeneous patient-derived tumor cell lines in anti-cancer drug screening system.

Abstract

We aimed to establish a fluorescence intensity-based colony area sweeping method by selecting the area of highest viability among patient-derived cancer cells (PDC) which has high tumor heterogeneity. Five gastric cancer cell lines and PDCs were screened with 24 small molecule compounds using a 3D micropillar/microwell chip. 100 tumor cells per well were immobilized in alginate, treated with the compounds, and then stained and scanned for viable cells. Dose response curves and IC50 values were obtained based on total or selected area intensity based on fluorescence. Unlike homogeneous cell lines, PDC comprised of debris and low-viability cells, which resulted in an inaccurate estimation of cell viability using total fluorescence intensity as determined by high IC50 values. However, the IC50 of these cells was lower and accurate when calculated based on the selected-colony-area method that eliminated the intensity offset associated with the heterogeneous nature of PDC. The selected-colony-area method was optimized to accurately predict drug response in micropillar environment using heterogeneous nature of PDCs.

• Authors: Jang Ho Cho, Ju-Sun Kim, Seung Tae Kim, Jung Yong Hong, Joon Oh Park, Young Suk Park, Do-Hyun Nam, Dong Woo Lee, Jeeyun Lee
• Journal: PloS one (PLoS One) Vol. 14 Issue 4 Pg. e0215080 ( 2019) ISSN: 1932-6203 [Electronic] United States
• PMID: 30995234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents

Topics

• Adult
• Aged
• Antineoplastic Agents (pharmacology)
• Cell Culture Techniques (methods)
• Cell Survival
• Drug Screening Assays, Antitumor (methods)
• Early Detection of Cancer
• Female
• High-Throughput Screening Assays (methods)
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (drug therapy, pathology)
• Stomach Neoplasms (drug therapy, pathology)
• Tumor Cells, Cultured