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Yichao Liu

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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      38P - Hedgehog pathway activation might mediate pemetrexed resistance in NSCLC cells (ID 330)

      12:30 - 13:00  |  Presenting Author(s): Yichao Liu

      • Abstract
      • Slides


      Lung cancer is the leading cause of death among all other malignancies. Despite the wide use and the high efficacy of immunotherapy, most patients with advanced or metastatic disease need chemotherapeutic treatment. Primary and acquired resistance to chemotherapeutic agents are the main cause of reduced overall survival. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemo resistance. Thus, this study aims at investigating the role of HH signalling in chemo resistant NSCLC cells.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      HCC827 NSCLC cells were treated with increasing sub-lethal doses of pemetrexed and vinorelbine to produce pemetrexed and vinorelbine resistant cells. RNA was isolated from both chemo resistant and naive cells. RT-qPCR was performed to evaluated mRNA gene expression. To measure cell growth capacity we used a MTT assay to evaluate the impact of the HH-inhibitor vismodegib in naïve and chemo resistant cell lines.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      Pemetrexed resistant cells showed clearly increased expression levels of most of HH signalling genes. The HH transcription factors GLI1, GLI2 and GLI3 were increased 3.7, 4.3 and 3.5 fold compared to non-resistant cells. The trans-membrane HH receptor PTCH1 showed to be elevated 2.4 fold and the ligand of HH signalling SSH revealed to be expressed 5.9 fold compared to naïve cells. However, vinorelbine resistant cells did not show a significant activation of HH signalling. Supporting these results pemetrexed resistant cells treated with the HH inhibitor vismodegib showed reduced proliferation compared to naïve cells treated with vismodegib.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      These are the first results of our study investigating the impact of HH signalling on chemo resistant NSCLC cells. In the case of pemetrexed resistance activation of HH pathway could play an important role to mediate this resistance. However, further investigation is needed to clarify the role of the HH pathway in NSCLC treatment.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      The authors.

      213f68309caaa4ccc14d5f99789640ad Funding

      Has not received any funding.

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.


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