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Article

Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma

  • Authors:
    • Yanmeng Kang
    • Mingjie Ding
    • Guangyan Tian
    • Haisheng Guo
    • Yunyan Wan
    • Zhouhong Yao
    • Bin Li
    • Dianjie Lin
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Respiratory Medicine, Jinan Children's Hospital, Jinan, Shandong 250022, P.R. China, Department of Neurology, Jinan Children's Hospital, Jinan, Shandong 250022, P.R. China, Department of Oncology, Dongying People's Hospital, Dongying 257091, P.R. China
  • Pages: 313-319
    |
    Published online on: April 26, 2013
       https://doi.org/10.3892/or.2013.2429
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Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive and conventional treatment-resistant tumor with a dismal prognosis. Among the three histological subtypes of MPM, the epithelioid is the most common type. Numb is considered as a tumor suppressor playing a critical role in controlling asymmetric cell division, maintenance of stem cell compartments, ubiquitination of specific substrates and regulating Notch-, Hedgehog- and TP53-activated pathways. The present study was designed to analyze the role of Numb in epithelioid MPM. We investigated the expression of Numb in 39 epithelioid MPM and 22 normal pleural tissues by immunohistochemistry. Furthermore, we overexpressed Numb in NCI-H2452, an epithelioid human MPM cell line, and investigated the effect of Numb overexpression on the proliferation, apoptosis and sensitivity to cisplatin in cells. The expression of Numb was significantly lower in MPM compared to the control group and Numb had an inverse correlation with the ki-67 labeling index. Loss of Numb expression was associated with poor prognosis in epithelioid MPM. Overexpression of Numb in NCI-H2452 cells significantly inhibited proliferation, promoted apoptosis and enhanced sensitivity to cisplatin. Moreover, Numb overexpression activated caspase-9 and caspase-3 through release of cytochrome c as well as downregulation of XIAP and survivin. We speculate that cytochrome c/caspase signaling is a possible mechanism through which Numb enhances the apoptosis of NCI-H2452 cells. These results suggest that Numb may be involved in epithelioid MPM development, and its upregulation may confer sensitivity to cisplatin, suggesting potential therapeutic options for MPM.
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Copy and paste a formatted citation
Spandidos Publications style
Kang Y, Ding M, Tian G, Guo H, Wan Y, Yao Z, Li B and Lin D: Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma. Oncol Rep 30: 313-319, 2013.
APA
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z. ... Lin, D. (2013). Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma. Oncology Reports, 30, 313-319. https://doi.org/10.3892/or.2013.2429
MLA
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z., Li, B., Lin, D."Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma". Oncology Reports 30.1 (2013): 313-319.
Chicago
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z., Li, B., Lin, D."Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma". Oncology Reports 30, no. 1 (2013): 313-319. https://doi.org/10.3892/or.2013.2429
Copy and paste a formatted citation
x
Spandidos Publications style
Kang Y, Ding M, Tian G, Guo H, Wan Y, Yao Z, Li B and Lin D: Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma. Oncol Rep 30: 313-319, 2013.
APA
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z. ... Lin, D. (2013). Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma. Oncology Reports, 30, 313-319. https://doi.org/10.3892/or.2013.2429
MLA
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z., Li, B., Lin, D."Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma". Oncology Reports 30.1 (2013): 313-319.
Chicago
Kang, Y., Ding, M., Tian, G., Guo, H., Wan, Y., Yao, Z., Li, B., Lin, D."Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma". Oncology Reports 30, no. 1 (2013): 313-319. https://doi.org/10.3892/or.2013.2429
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