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Yu Zhang



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    P1 - Poster Viewing (ID 5)

    • Event: NACLC 2019
    • Type: Poster Session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 10/11/2019, 16:45 - 18:00, Exhibit Hall
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      P1.04 - Combined Effects of HDAC Inhibitor and Metalloproteinase Inhibitor on Invasion and Growth of Non-Small Cell Lung Cancer (ID 38)

      16:45 - 18:00  |  Presenting Author(s): Yu Zhang

      • Abstract

      Background:
      Histone deacetylase inhibitor ?HDACI?is known. HDAC inhibitors effect on tumor cell migration, invasion, metastasis and anti-tumor angiogenesis has also been confirmed. Histone deacetylase inhibitors can usually be divided into Two major categories and FDA-approved clinical drugs are now mainly inhibiting Zn2+-dependent histone deacetylases. Matrix metalloproteinase, a large family of matrix metalloproteinases, can almost degrade various protein components in ECM, destroy the histological barrier of tumor cell invasion, play a key role in tumor invasion and metastasis, and thus in tumor The role of infiltration and transfer has received increasing attention and is considered to be the main proteolytic enzyme in the process. Tissue inhibitor of matrix metalloproteinases (TIMPs) are specific inhibitors of MMPs, which effectively inhibit the collagen and gelatin decomposition activities of MMP and inhibit metastasis and invasion of cancer cells. It has been reported that HDAC inhibitors can reduce the activity of MMP leading to inhibit tumor activity and growth . However, little is known about the combined effects of HDAC inhibitors and MMP inhibitors on tumor invasion and metastasis.


      Method:
      The lung cancer cell line A549 was cultured in vitro, and HDAC inhibitor (SAHA), MMP inhibitor (clorhexidine, CHX), SAHA and CHX were added to observe the cell viability, viable cell concentration and mitosis of the three groups. At the same time, we used 30 BALB/c mice divided into three groups, lung cancer cells were injected into the lungs, and HDAC inhibitors (SAHA) and MMP inhibitors (CHORhexidine, CHX) were administered after 21 days or 30 days of lung tumor formation. In combination with SAHA and CHX, lung tissue and blood samples were taken on the 3rd day, 7th day, 14th day, 30th day after the treatment and the natural death of the mice. The pathological tissue sections were examined, and the tumor activity was observed by electron microscopy. qPCR, HDAC activity, MMP, CDC, and the like. Tumor markers in the blood: carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), squamous cell carcinoma antigen (SCC), cytokeratin 21-1 (Cyfra21-1), neuron-specific enolase ( NSE), basic fetal protein (BFP).


      Results:
      HDAC inhibitors combined with MMP inhibitor group had longer survival time (>6 months), lung tumors were significantly reduced, and no metastasis occurred for a longer period of time (>30 days). The other two groups also had certain tumor growth. Inhibition.


      Conclusion:
      HDAC inhibitors combined with MMP inhibitors are an effective combination therapy, but long-term treatment and complications require more research to verify.