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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells

  • Authors:
    • Li Lin
    • David Jou
    • Yina Wang
    • Haiyan Ma
    • Tianshu Liu
    • James Fuchs
    • Pui-Kai Li
    • Jiagao Lü
    • Chenglong Li
    • Jiayuh Lin
  • View Affiliations / Copyright

    Affiliations: Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China, Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH 43205, USA, Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
    Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2265-2274
    |
    Published online on: October 12, 2016
       https://doi.org/10.3892/ijo.2016.3728
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Abstract

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+). STAT3 activation and the effects of STAT3 inhibition by STAT3 inhibitors, LLL12, FLLL32, and Stattic in ALDH+ and CD44+/CD24+ cells were examined. Our results showed that ALDH+ and CD44+/CD24+ pancreatic cancer stem-like cells expressed higher levels of phosphorylated STAT3, an active form of STAT3, compared to ALDH-negative (ALDH-) and CD44-negative/CD24-negative (CD44-/CD24-) pancreatic cancer cells, suggesting that STAT3 is activated in pancreatic cancer stem-like cells. Small molecular STAT3 inhibitors inhibited STAT3 phosphorylation, STAT3 downstream target gene expression, cell viability, and tumorsphere formation in ALDH+ and CD44+/CD24+ cells. Our results indicate that STAT3 is a novel therapeutic target in pancreatic cancer stem-like cells and inhibition of activated STAT3 in these cells by STAT3 inhibitors may offer an effective treatment for pancreatic cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Lin L, Jou D, Wang Y, Ma H, Liu T, Fuchs J, Li P, Lü J, Li C, Lin J, Lin J, et al: STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. Int J Oncol 49: 2265-2274, 2016.
APA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J. ... Lin, J. (2016). STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. International Journal of Oncology, 49, 2265-2274. https://doi.org/10.3892/ijo.2016.3728
MLA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49.6 (2016): 2265-2274.
Chicago
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49, no. 6 (2016): 2265-2274. https://doi.org/10.3892/ijo.2016.3728
Copy and paste a formatted citation
x
Spandidos Publications style
Lin L, Jou D, Wang Y, Ma H, Liu T, Fuchs J, Li P, Lü J, Li C, Lin J, Lin J, et al: STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. Int J Oncol 49: 2265-2274, 2016.
APA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J. ... Lin, J. (2016). STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. International Journal of Oncology, 49, 2265-2274. https://doi.org/10.3892/ijo.2016.3728
MLA
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49.6 (2016): 2265-2274.
Chicago
Lin, L., Jou, D., Wang, Y., Ma, H., Liu, T., Fuchs, J., Li, P., Lü, J., Li, C., Lin, J."STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells". International Journal of Oncology 49, no. 6 (2016): 2265-2274. https://doi.org/10.3892/ijo.2016.3728
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