Author of

• 16751

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  P1.05 - Poster Session with Presenters Present (ID 457)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Early Stage NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 16764

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    P1.05-013 - Lung Tumorspheres as a Platform for Testing New Therapeutic Strategies in Non-Small Cell Lung Cancer (ID 4848)

    14:30 - 14:30  |  Author(s): E. Escorihuela
    • Abstract

    Background:
    Resistance to treatment is one of the causes influencing the high mortality of lung cancer. This feature seems to be linked to a subpopulation known as Cancer Stem Cells (CSCs), which are able to grow as spheroids (suspension culture). The aim of the study was to obtain tumorspheres from lung cancer cell lines and to use them as an in vitro platform for drug screening.
    
    Methods:
    Cells from lung cancer cell lines (A549, H1650, PC9, H460 and H358) were grown in monolayer and as spheroids. Cultured cells were used: (i) to compare the cytotoxic effect of anticancer drugs in adherent vs lung-tumorspheres (ii) to perform a high-throughput screening with a commercial chemical library (Prestwick) and (iii) to analyze the citotoxicity of specific inhibitors of Wnt, Hedgehog and Notch pathways. Briefly, cells were plated at the desired density in 200 μl of medium in 96-well plates and compounds were added at 4 different concentrations (n=3). Cell viability was measured after 48 and 72h, using MTS Assay. Cell viability was normalized to the respective mock-treated control cells and presented as percentage of control.
    
    Results:
    Cells cultured in serum-free conditions were able to form spheroids, such as stem-like cells. Under these culture conditions, classical anticancer drugs (cisplatin, paclitaxel, vinorelbine and pemetrexed) exhibited mild or null cytotoxic effects on A549, H1650, PC9, H460 and H358 spheroids. Moreover, we performed a high-throughput screening with Prestwick library and remarkably, three compounds reduced the number of viable cancer cells. As regards ‘stemness’ inhibitors, Wnt (IWP2 and XAV939) and Hedgehog inhibitors (Vismodegib) show high activity against tumorspheres (p<0.05), suggesting them as possible therapeutic strategies in NSCLC
    
    Conclusion:
    Our data suggest that lung-tumorspheres showed resistance to classical anticancer drugs, strengthening its possible use as a short-term culture platform for a simple, and cost- effective screening to investigate novel therapeutic approaches. In this setting, some compounds were identified as promising therapeutic agents on lung tumorspheres, but confirmatory data are still necessary. This project was supported by [RD12/0036/0025] from RTICC, SEOM 2012, [PI12-02838 and PI15-00753] from ISCIII