Author of

• 17398

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  P2.01 - Poster Session with Presenters Present (ID 461)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17410

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    P2.01-012 - Acquired Chemotherapy Resistance in vitro: miRNA Profiles of Chemotherapy Resistant Squamous Lung Cancer Cell Lines (ID 4160)

    14:30 - 14:30  |  Author(s): V.M. Howell
    • Abstract

    Background:
    Lung cancer is the leading cause of cancer death worldwide. 25 -30% of lung cancers are histologically squamous cell carcinomas (SCC). Despite recent advances in immunotherapy for lung SCC, traditional cytotoxic chemotherapies currently remain the mainstay of treatment. However, over the course of treatment, patients with lung SCC inevitably acquire chemotherapy resistance. This results in poor overall survival of advanced stage lung SCC of only 9 to 11 months. Repetitive exposure of lung cancer cell lines to chemotherapeutic drugs enables investigation of molecular mechanisms of acquired chemotherapy resistance in vitro. We are studying the role of miRNAs in this process. MiRNAs are small non-coding nucleic acids that regulate gene expression. They are involved in numerous cellular pathways, including therapy resistance. MiRNA serve as biomarkers and have recently become therapeutic targets or therapeutics themselves.
    
    Methods:
    We induced chemotherapy resistance in lung SCC cell lines LUDLU-1, Calu-1, SK-MES-1 in vitro by repetitive drug treatment over a period of 6 – 12 months. Agents used to develop resistance included Cisplatin, Gemcitabine, Paclitaxel and Vinorelbine. Cell viability after 3 days of chemotherapy treatment was measured by MTT assay and drug dose causing a 50% growth inhibition (IC~50~) was calculated. Total RNA including miRNA was extracted. Expression of 754 miRNA was measured by TaqMan OpenArray Human MicroRNA array.
    
    Results:
    After 15 -25 cycles of chemotherapy lung SCC resistant cells showed a statistically significant increase in IC~50~ values: Cisplatin up to 12.4 (n-fold); Gemcitabine 40.2 – absolute resistance (n-fold); Paclitaxel 30.9 – 110.1 (n-fold); Vinorelbine 4.8 -19.3 (n-fold). Resistance was stable and passed on to daughter cells. MiRNA expression of resistant cells was compared to parental, drug sensitive cells and is illustrated by heatmaps and volcano plots. Analysis of expression patterns revealed upregulation and downregulation of specific miRNAs in drug resistant cells. We are currently investigating the function of these dysregulated miRNAs in promoting chemotherapy resistance. Further, we are testing if certain miRNA are suitable targets to improve chemotherapy response.
    
    Conclusion:
    We identified changes of miRNA expression patterns after induction of chemotherapy resistance with various drugs used for lung SCC treatment. These findings may lead to development of new predictive biomarkers and to new miRNA-based drugs.