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Article

Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine

  • Authors:
    • Hong-Quan Duong
    • Yong Weon Yi
    • Hyo Jin Kang
    • Young Bin Hong
    • Wenxi Tang
    • Antai Wang
    • Yeon-Sun Seong
    • Insoo Bae
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA, Department of Biostatistics, Columbia University, New York, NY, USA, Department of Nanobiomedical Science and WCU (World Class University) Research Center of Nanobiomedical Science, Dankook University, Cheonan, Republic of Korea
  • Pages: 959-969
    |
    Published online on: December 23, 2013
       https://doi.org/10.3892/ijo.2013.2229
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Abstract

We describe the potential benefit of PIK-75 in combination of gemcitabine to treat pancreatic cancer in a preclinical mouse model. The effect of PIK-75 on the level and activity of NRF2 was characterized using various assays including reporter gene, quantitative PCR, DNA-binding and western blot analyses. Additionally, the combinatorial effect of PIK-75 and gemcitabine was evaluated in human pancreatic cancer cell lines and a xenograft model. PIK-75 reduced NRF2 protein levels and activity to regulate its target gene expression through proteasome-mediated degradation of NRF2 in human pancreatic cancer cell lines. PIK-75 also reduced the gemcitabine-induced NRF2 levels and the expression of its downstream target MRP5. Co-treatment of PIK-75 augmented the antitumor effect of gemcitabine both in vitro and in vivo. Our present study provides a strong mechanistic rationale to evaluate NRF2 targeting agents in combination with gemcitabine to treat pancreatic cancers.
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Copy and paste a formatted citation
Spandidos Publications style
Duong H, Yi YW, Kang HJ, Hong YB, Tang W, Wang A, Seong Y and Bae I: Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol 44: 959-969, 2014.
APA
Duong, H., Yi, Y.W., Kang, H.J., Hong, Y.B., Tang, W., Wang, A. ... Bae, I. (2014). Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. International Journal of Oncology, 44, 959-969. https://doi.org/10.3892/ijo.2013.2229
MLA
Duong, H., Yi, Y. W., Kang, H. J., Hong, Y. B., Tang, W., Wang, A., Seong, Y., Bae, I."Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine". International Journal of Oncology 44.3 (2014): 959-969.
Chicago
Duong, H., Yi, Y. W., Kang, H. J., Hong, Y. B., Tang, W., Wang, A., Seong, Y., Bae, I."Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine". International Journal of Oncology 44, no. 3 (2014): 959-969. https://doi.org/10.3892/ijo.2013.2229
Copy and paste a formatted citation
x
Spandidos Publications style
Duong H, Yi YW, Kang HJ, Hong YB, Tang W, Wang A, Seong Y and Bae I: Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. Int J Oncol 44: 959-969, 2014.
APA
Duong, H., Yi, Y.W., Kang, H.J., Hong, Y.B., Tang, W., Wang, A. ... Bae, I. (2014). Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. International Journal of Oncology, 44, 959-969. https://doi.org/10.3892/ijo.2013.2229
MLA
Duong, H., Yi, Y. W., Kang, H. J., Hong, Y. B., Tang, W., Wang, A., Seong, Y., Bae, I."Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine". International Journal of Oncology 44.3 (2014): 959-969.
Chicago
Duong, H., Yi, Y. W., Kang, H. J., Hong, Y. B., Tang, W., Wang, A., Seong, Y., Bae, I."Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine". International Journal of Oncology 44, no. 3 (2014): 959-969. https://doi.org/10.3892/ijo.2013.2229
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