A p110δ-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-κB

  • Authors:
    • Ga Bin Park
    • Yoon Hee Chung
    • Jee-Yeong Jeong
    • Daejin Kim
  • View Affiliations

  • Published online on: March 21, 2017     https://doi.org/10.3892/ijo.2017.3923
  • Pages: 1711-1720
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Abstract

Epstein-Barr virus (EBV) infection is closely related to carcinogenesis of various cancers, and is also associated with the development of drug resistance in cancer stem cells. However, in EBV-positive cancer cells, the mechanistic details of the downstream signaling and the connection of PI3K with the NF-κB pathway for development of drug resistance remain controversial. Diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM) cells infected by EBV display drug resistance-related proteins (MDR1, MRP1 and MRP2) and stem cell markers (OCT4 and SOX2). EBV-infected HT (HT/EBV) and H929 (H929/EBV) cells activated p110δ expression, but downregulated the expression of p110α and p110β. A combination of CAL-101, a p110δ-specific inhibitor, with bortezomib treatment of HT/EBV cells synergistically suppressed proliferation, reduced levels of drug resistance-related proteins, activated caspase cleavage and recovered expression of p110α/p110β. Additionally, co-treatment with CAL-101 and bortezomib attenuated the expression of OCT4 and SOX2 via inhibition of activated NF-κB. Co-treatment with CAL-101 and bortezomib also attenuated drug resistance and NF-κB activity of EBV-infected H929 cells. Our results provide supportive evidence for the clinical application of CAL-101 and bortezomib to treat EBV-infected hematologic cancer.
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May-2017
Volume 50 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Park GB, Chung YH, Jeong J and Kim D: A p110δ-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-κB. Int J Oncol 50: 1711-1720, 2017.
APA
Park, G.B., Chung, Y.H., Jeong, J., & Kim, D. (2017). A p110δ-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-κB. International Journal of Oncology, 50, 1711-1720. https://doi.org/10.3892/ijo.2017.3923
MLA
Park, G. B., Chung, Y. H., Jeong, J., Kim, D."A p110δ-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-κB". International Journal of Oncology 50.5 (2017): 1711-1720.
Chicago
Park, G. B., Chung, Y. H., Jeong, J., Kim, D."A p110δ-specific inhibitor combined with bortezomib blocks drug resistance properties of EBV-related B cell origin cancer cells via regulation of NF-κB". International Journal of Oncology 50, no. 5 (2017): 1711-1720. https://doi.org/10.3892/ijo.2017.3923