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    P63 - Tumor Biology and Systems Biology - Basic and Translational Science - Metastases (ID 201)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P63.02 - CDK9 Mediate Lung Adenocarcinoma A549 Cell Brain Metastasis in Murine Model (ID 1055)

      00:00 - 00:00  |  Presenting Author(s): Bo Tian

      • Abstract
      • Slides

      Introduction

      Lung cancer is the leading cause of cancer-related mortality worldwide. Most lung cancer patients with brain metastases have very poor prognosis. The most common type of brain metastases is from human lung adenocarcinoma. Although cyclin-dependent kinase (CDK) 9 has an established pathogenic role in various cancers, its function in lung cancer brain metastasis remains poorly defined.

      Methods

      We established A549 BrM3 cell line from a parental cell line A549 (K-rasG12S). And investigated the expression of CDK9 in 3 matched brain metastasis and lung adenocarcinoma tissues, and three matched brain metastatic lung adenocarcinoma cell lines H2030-BrM3, PC9-BrM3, A549-BrM3 and their parental cell lines H2030, PC9, and A549. And then stable expression of CDK9 shRNA knock-down in the luciferase labeled tumor cell lines were tested in vitro and the brain metastasis models in vivo.

      Results

      We found that compared with primary lung cancer IHC, brain metastasis cancer had strong CDK9 stain and staining localized at nuclei. And we found that metastatic NSCLC cell lines H2030-BrM3, PC9-BrM3, A549-BrM3 had a significantly increased CDK9 expression compared to their parental cell lines (P<0.05). Inhibition of CDK9 by shRNA significantly decreased expression in downstream genes CYR61 in A549-BrM3 cells (P<0.05). And mice inoculated with CDK9 shRNA-transfected A549-BrM3 cells had significantly decreased metastatic tumor burden and survived longer than control mice (P<0.05).

      Conclusion

      Our results suggest that CDK9 plays an important role in promoting lung adenocarcinoma brain metastasis and that direct inhibition of CDK9 by shRNA suppresses A549-BrM3 cell brain metastasis in a murine model.

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