Multilayered Cultures of NSCLC cells grown at the Air-Liquid Interface allow the efficacy testing of inhaled anti-cancer drugs

Scientific Reports
Dania MoviaAdriele Prina-Mello

Abstract

Evidence supports the advantages of inhalation over other drug-administration routes in the treatment of lung diseases, including cancer. Although data obtained from animal models and conventional in vitro cultures are informative, testing the efficacy of inhaled chemotherapeutic agents requires human-relevant preclinical tools. Such tools are currently unavailable. Here, we developed and characterized in vitro models for the efficacy testing of inhaled chemotherapeutic agents against non-small-cell lung cancer (NSCLC). These models recapitulated key elements of both the lung epithelium and the tumour tissue, namely the direct contact with the gas phase and the three-dimensional (3D) architecture. Our in vitro models were formed by growing, for the first time, human adenocarcinoma (A549) cells as multilayered mono-cultures at the Air-Liquid Interface (ALI). The in vitro models were tested for their response to four benchmarking chemotherapeutics, currently in use in clinics, demonstrating an increased resistance to these drugs as compared to sub-confluent monolayered 2D cell cultures. Chemoresistance was comparable to that detected in 3D hypoxic tumour spheroids. Being cultured in ALI conditions, the multilayered monocultures d...Continue Reading

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Citations

Jun 1, 2019·PloS One·Aneetta E KuriakoseJyothi U Menon
Apr 23, 2020·International Journal of Molecular Sciences·Ruben Mercado SantosWen Cai Zhang
Jun 26, 2020·Frontiers in Bioengineering and Biotechnology·Dania MoviaAdriele Prina-Mello
Jun 14, 2020·Colloids and Surfaces. B, Biointerfaces·Maroua Ben HaddadaJolanda Spadavecchia
Nov 17, 2020·Frontiers in Bioengineering and Biotechnology·Aylin CidemHui Xin Ong
Jul 7, 2021·Alternatives to Laboratory Animals : ATLA·Bhumika SinghJohn Malcolm Wilkinson
Jan 26, 2022·Molecular Biology Reports·Swagata RoySatarupa Banerjee

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Methods Mentioned

BETA
Assay
flow cytometry
Enzyme
Protein Assay

Software Mentioned

- Pad
Graph
ImageJ
- Pad Prism
Zeiss Zen software

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