Open Access

Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells

  • Authors:
    • Hong-Quan Duong
    • Jae Seok Hwang
    • Hee Jeong Kim
    • Hyo Jin Kang
    • Yeon-Sun Seong
    • Insoo Bae
  • View Affiliations

  • Published online on: June 12, 2012     https://doi.org/10.3892/ijo.2012.1516
  • Pages: 855-861
  • Copyright: © Duong et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Gemcitabine (GEM) is the front-line standard chemotherapy used for the treatment of pancreatic cancer; however, chemoresistance to GEM remains the major obstacle to the successful control of this disease. Both the expression levels and activity of aldehyde dehydrogenase 1A1 (ALDH1A1) are important features of tumor-initiating and/or cancer stem cell properties in multiple types of human cancer. As one of the intrinsic properties of cancer stem cells is drug resistance, in this study, we examined the correlation between the level and activity of endogenous ALDH1A1 and GEM resistance in the MIA PaCa-2 cell line that contains high expression levels and activity of ALDH1A1. We used small interfering RNAs (siRNAs) to deplete ALDH1A1 and investigate its potential role in conferring GEM resistance. The ALDH1A1 knockdown markedly reduced ALDH1A1 expression and activity and inhibited cell proliferation. Moreover, the combination of ALDH1A1-siRNA and GEM significantly decreased cell viability, increased apoptotic cell death and increased the accumulation of cells at the S-phase compared to the controls. Our data also demonstrated that ALDH1A1 expression and activity were significantly higher in the GEM-resistant MIA PaCa-2 cell line (MIA PaCa-2/GR), compared to the parental MIA PaCa-2 cell line (MIA PaCa-2/P). In the MIA PaCa-2/GR cells, the combination of ALDH1A1-siRNA and GEM also showed a significant decrease in cell viability and an increase in apoptotic cell death, emphasizing the importance of ALDH1A1 in both intrinsic and acquired GEM resistance. This potentially powerful combination treatment of ALDH1A1-siRNA and GEM warrants further investigation as an effective therapeutic regimen to overcome the resistance of pancreatic cancer to GEM.
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September 2012
Volume 41 Issue 3

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

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Spandidos Publications style
Duong H, Hwang JS, Kim HJ, Kang HJ, Seong Y and Bae I: Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. Int J Oncol 41: 855-861, 2012.
APA
Duong, H., Hwang, J.S., Kim, H.J., Kang, H.J., Seong, Y., & Bae, I. (2012). Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. International Journal of Oncology, 41, 855-861. https://doi.org/10.3892/ijo.2012.1516
MLA
Duong, H., Hwang, J. S., Kim, H. J., Kang, H. J., Seong, Y., Bae, I."Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells". International Journal of Oncology 41.3 (2012): 855-861.
Chicago
Duong, H., Hwang, J. S., Kim, H. J., Kang, H. J., Seong, Y., Bae, I."Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells". International Journal of Oncology 41, no. 3 (2012): 855-861. https://doi.org/10.3892/ijo.2012.1516