Dataset Information

Evaluation of assays for drug efficacy in a three-dimensional model of the lung.

ABSTRACT:

Background

The focus of the outlined work is the establishment of a three-dimensional lung model for various drug-screening applications.

Methods

The non-small cell lung cancer (NSCLC) cell line Colo699 was cultivated as monolayer (2D) on plates for 5 days or as microtissues (3D) using a hanging-drop system for 5 and 10 days. Cells and microtissues were treated with afatinib (10-80 µM), cisplatin (100-800 µM) or vinorelbine (25-200 µM) for 24 or 48 hours (h). Cell proliferation and viability were analysed by intra-cellular adenosine triphosphate (ATP) and lactate dehydrogenase release (LDH) assays, annexin V/propidium iodide (PI) staining, and cell cycle determination. Microtissue morphology and size, as well as cell death were evaluated via phase contrast microscopy.

Results

Our results demonstrate the valid determination of viability and cell death using established assays in the 3D system for drug testing. The comparison of ATP, LDH and cytometry data showed moderate (0.40) to very strong (0.99) correlations. Thereby, we observed partially significant differences in drug efficacy between microtissues and 2D cultures dependent from the applied treatment and read-out method. Altogether, microtissues developed resistance to cisplatin and vinorelbine; but remained more vulnerable to afatinib. These findings were confirmed with microscopy.

Conclusion

In summary, we established an NSCLC 3D test system with multiple assays compatible for drug-testing applications of substances with different mechanisms of action. In addition, our data support the usage of microtissues as more accurate tools for drug-efficacy testing with the possibility of long-term cultivation and treatment.

SUBMITTER: Huber JM

PROVIDER: S-EPMC4978763 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

Evaluation of assays for drug efficacy in a three-dimensional model of the lung.

Huber Julia M JM Amann Arno A Koeck Stefan S Lorenz Edith E Kelm Jens M JM Obexer Petra P Zwierzina Heinz H Gamerith Gabriele G

Journal of cancer research and clinical oncology 20160716 9

<h4>Background</h4>The focus of the outlined work is the establishment of a three-dimensional lung model for various drug-screening applications.<h4>Methods</h4>The non-small cell lung cancer (NSCLC) cell line Colo699 was cultivated as monolayer (2D) on plates for 5 days or as microtissues (3D) using a hanging-drop system for 5 and 10 days. Cells and microtissues were treated with afatinib (10-80 µM), cisplatin (100-800 µM) or vinorelbine (25-200 µM) for 24 or 48 hours (h). Cell proliferation an ...[more]

PMID: 27424189

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Dataset Information

Evaluation of assays for drug efficacy in a three-dimensional model of the lung.

Background

Methods

Results

Conclusion

Publications

Evaluation of assays for drug efficacy in a three-dimensional model of the lung.

Similar Datasets

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