Abstract
Introduction: Due to their metabolic properties, brown (BAT) and white adipose tissue (WAT) may play a role in the development of resistance to chemotherapy in lung cancer (LC) cells.
Aims: To this end, we aimed to find out whether adipose tissue directly interacts with LC cells in a coculture system to reduce therapy efficacy.
Methods: LC cell lines (H322, A549, H1650, PC9) were each cocultured with undifferentiated preadipocytes, BAT or WAT (3T3-L1). The in vitro coculture system consisted of a culture plate and a horizontal insert put in with a microporous membrane (0.4 µm) allowing for cell-cell interactions via soluble factors between upper and lower cell compartment. To assess resistance to the chemotherapeutics cisplatin, gefitinib, or osimertinib, we analysed cell proliferation and apoptosis by using the colorimetric MTT tetrazolium reduction assay or the flow cytometric annexin V FITC / propidium iodide assay, respectively.
Results: We found reduced efficacy of gefitinib or osimertinib when H322, A549, and H1650 cells were cocultured with adipocytes. These effects were distinctively pronounced for WAT coculture in A549 cells and for BAT in H322 cells. Likewise, we found less apoptotic A549 and H322 cells when cocultured with adipocytes and treated with osimertinib, while WAT led to less apoptotic A549 cells then BAT. Flow cytometric assessment of viable cells via annexin confirmed MTT results.
Conclusions: The coculture with brown and white tissue reduces the efficacy of gefitinib and osimertinib in LC cells in terms of lower growth inhibition, higher proliferation and lower apoptosis. The coculture of adipose tissue can lead to resistance to targeted therapy in LC cells.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1764.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020