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Ming-Shyan Huang



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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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      34P - Impacts of HDAC2 inhibition on lung cancer treatment (ID 541)

      12:30 - 13:00  |  Author(s): Ming-Shyan Huang

      • Abstract

      Background

      Approximately 80% of lung cancer is non-small cell lung cancer (NSCLC) with a median survival time of 8 to 10 months. It is critical and urgent to find the effective interventions for patients suffering from NSCLC. Histone deacetylase 2 (HDAC2) is increasingly associated with development of several solid tumors. However, its role in lung cancer remained mostly lacking.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      Immunohistochemistry was used to analyze the distribution patterns of HDAC2 protein in lung cancer and the results were further statistically correlated with clinicopathological characteristics and survival rate. XTT, invasion assay, flowcytometry, immunoblotting, and immunoprecipitation were used to explore the bio-impacts and underlying mechanisms of HDAC2 and its interplay with nicotine in lung cancer cells.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      The Kaplan–Meier plotter shows that 1926 lung cancer patients with high HDAC2 mRNA levels will have a poor overall survival rate (p = 0.004). Increased HDAC2 mRNA expression predicts an improved overall survival of non-smoker patient group (p = 0.018) but not that of smoker patient group. Further immunohistochemistry showed similar results (p < 0.001). Intriguingly, this association seen in smoker and non-smoker groups was demonstrated in only squamous cell lung cancer, providing the specific interplay between HDAC2 and carcinogenic content of cigarette. Treatment with nicotine induced the NO production through rapidly increasing NOS2 expression and HDAC2 was subsequently nitrosylated. Knockdown of HDAC2 reduced nicotine-induced NOS2 expression and invasive activity. Ectopic HDAC2 overexpression enhanced nicotine-mediated NOS2 induction. Interestingly, ectopic overexpression of Cys262/274Ala HDAC2 mutant, un-nitrosylated, inhibited the invasive activity. HDAC2 specific siRNA and inhibitor enhanced the cytotoxicity of cisplatin and abolished the cisplatin-mediated cyclin B1 induction.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Our results implicated that HDAC2 might be required for cigarette carcinogenic content-mediated advanced development or treatment failure in lung cancer. NOS2 provides the link between nicotine and HDAC2 in lung cancer. Inhibition of HDAC2 activity may increase therapeutic effects of cisplatin-based treatments in NSCLC.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      Yao-Tsung Yeh.

      213f68309caaa4ccc14d5f99789640ad Funding

      MOST, Taiwan (R.O.C).

      682889d0a1d3b50267a69346a750433d Disclosure

      All authors have declared no conflicts of interest.

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