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γ-Secretase inhibitor, DAPT inhibits self-renewal and stemness maintenance of ovarian cancer stem-like cells in vitro

  • Original Article
  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

The Notch signaling pathway plays an important role in the stem cell signaling network and contributes to tumorigenesis. However, the functions of Notch signaling in ovarian cancer stem cells (OCSCs) are not well understood. We aimed to investigate the effects of Notch blockade on self-renewal and stemness maintenance of OCSCs.

Methods

Ovarian cancer stem-like cells were enriched from ovarian cancer cell lines in serum-free medium. A γ-secretase inhibitor, (DAPT), was used to block Notch signaling. MTT assays were performed to assess self-renewal and proliferation inhibition, flow cytometry was performed to analyze cell surface marker and immunofluorescence, Western Blot and Real-time RT-PCR assays were performed to detect Oct4 and Sox2 protein and mRNA expression of the Ovarian cancer stem-like cells treated with DAPT.

Results

Notch blockade markedly inhibits self-renewal and proliferation of ovarian cancer stem-like cells, significantly downregulates the expression of OCSCs-specific surface markers, and reduces protein and mRNA expression of Oct4 and Sox2 in OCSC-like cells.

Conclusion

Our results suggest that Notch signaling is not only critical for the self-renewal and proliferation of OCSCs, but also for the stemness maintenance of OCSCs. The γ-secretase inhibitor is a promising treatment targeting OCSCs.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, the First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Li-yu Jiang, Xiao-lei Zhang, Ping Du & Jian-hua Zheng

Authors
  1. Li-yu Jiang
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  2. Xiao-lei Zhang
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  3. Ping Du
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  4. Jian-hua Zheng
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Corresponding author

Correspondence to Jian-hua Zheng.

Additional information

This work was supported by a grant from the Heilongjang Province Science and Technology Commission of China (No. GB07C32304)

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Jiang, Ly., Zhang, Xl., Du, P. et al. γ-Secretase inhibitor, DAPT inhibits self-renewal and stemness maintenance of ovarian cancer stem-like cells in vitro . Chin. J. Cancer Res. 23, 140–146 (2011). https://doi.org/10.1007/s11670-011-0140-1

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  • DOI: https://doi.org/10.1007/s11670-011-0140-1

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