Author of

• 20177

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  P2.13 - Radiology/Staging/Screening (ID 714)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Radiology/Staging/Screening
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23470

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    P2.13-001 - Herbal Compound as a Potential Lead Targets Lung Cancer Stem Cells (ID 7534)

    09:30 - 09:30  |  Presenting Author(s): Pei-Jung Lee
    • Abstract

    Background:
    Cancer stem cells (CSCs) have been proposed to be responsible for tumor initiating, drug resistance, metastasis, and recurrence. Many novel therapeutic strategies have been designed to target and eliminate CSCs. According to our previous study, we have established a model of CSCs and cancer associated fibroblasts (CAFs) co-culture system for anti-CSCs drug screening. Here, we report one of the potential hits screened via this platform and the anti-CSCs activity was further investigated both in vitro and in vivo.
    
    Method:
    Human lung CSCs and CAFs were primary cultured from patient with lung adenocarcinoma according to our previous study. Image–based high content screening system was used to analyze different parameters after drug treatment. Tumorogenicity and self-renew ability are examined by sphere forming ability. Aldehyde dehydrogenase (ALDH) activity was used to analyze stem cell population by flow cytometry. The expression level of stemness-related genes, Nanog, Oct3/4 and Sox2 were validated by real-time reverse transcriptase Q-PCR. The efficacy of the lead on tumor growth was examined by the xenograft model. Lung cancer stemness markers of the xenograft tumor tissues were also evaluated by immunohistochemistry.
    
    Result:
    Using the CSC/CAF co-culture model with the image–based high content screening system to screen over one thousands of compounds, we have identified aloe-emodin (AE), an anthraquinone isolated from traditional herbs (e.g., Aloe vera), shows higher potency on lung CSCs (under 1 µM dosage) and relative selection for targeting on the cancer cell lines with the IC~50~ less twenty µM; compared to normal human bronchial epithelium cells and human normal fibroblast represented by IC~50~ (26.77 µM v.s. 39.13 µM). The level of stemness markers, Nanog, Sox2 and Oct3/4 were significantly down-regulated after AE treatment compared to cisplatin treatment. AE could suppress tumor initiating abilities and self-renew capacities by inhibiting the tumorous sphere forming in CL152 ALDH[+] cells. Besides, AE could inhibit ALDH population in CL152 cells (40% reduced). Also, the AE can inhibit the cisplatin-induced ALDH population as well. Furthermore, we found that the combination treatment of AE and cisplatin could inhibit tumor growth as comparing to cisplatin treatment in subcutaneous xenograft models in NOD/SCID mice, whereas, AE can significantly inhibit the level of Nanog in mice tumor tissues.
    
    Conclusion:
    According to these results, AE is a potential lead targeting on lung CSCs. To discover the pharmacological mechanism of AE on CSCs will be helpful to develop new strategy for lung cancer therapy.