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Article Open Access

Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization

  • Authors:
    • Tao Yan
    • Hai‑Ying Li
    • Jian‑Song Wu
    • Qiang Niu
    • Wei‑Hong Duan
    • Qing‑Zeng Han
    • Wang‑Ming Ji
    • Tao Zhang
    • Wei Lv
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, The General Hospital of The PLA Rocket Force, Beijing 100088, P.R. China, Surgical Department, Qinghe County Central Hospital, Qinghe, Xingtai, Hebei 054800, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5400-5408
    |
    Published online on: August 28, 2017
       https://doi.org/10.3892/ol.2017.6836
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Abstract

Pancreatic cancer rapidly acquires resistance to chemotherapy resulting in its being difficult to treat. Gemcitabine is the current clinical chemotherapy strategy; however, owing to gemcitabine resistance, it is only able to prolong the life of patients with pancreatic cancer for a limited number of months. Understanding the underlying molecular mechanisms of gemcitabine resistance and selecting a suitable combination of agents for the treatment of pancreatic cancer is required. Astaxanthin (ASX) is able to resensitize gemcitabine‑resistant human pancreatic cancer cells (GR‑HPCCs) to gemcitabine. ASX was identified to upregulate human equilibrative nucleoside transporter 1 (hENT1) and downregulate ribonucleoside diphosphate reductase (RRM) 1 and 2 to enhance gemcitabine‑induced cell death in GR‑HPCCs treated with gemcitabine, and also downregulates TWIST1 and ZEB1 to inhibit the gemcitabine‑induced epithelial‑mesenchymal transition (EMT) phenotype in GR‑HPCCs and to mediate hENT1, RRM1 and RRM2. Furthermore, ASX acts through the hypoxia‑inducible factor 1α/signal transducer and activator of transcription 3 signaling pathway to mediate TWIST1, ZEB1, hENT1, RRM1 and RRM2, regulating the gemcitabine‑induced EMT phenotype and gemcitabine‑induced cell death. Co‑treatment with ASX and gemcitabine in a tumor xenograft model induced by GR‑HPCCs supported the in vitro results. The results of the present study provide a novel therapeutic strategy for the treatment of gemcitabine‑resistant pancreatic cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Yan T, Li HY, Wu JS, Niu Q, Duan WH, Han QZ, Ji WM, Zhang T and Lv W: Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization. Oncol Lett 14: 5400-5408, 2017.
APA
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q. ... Lv, W. (2017). Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization. Oncology Letters, 14, 5400-5408. https://doi.org/10.3892/ol.2017.6836
MLA
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q., Ji, W., Zhang, T., Lv, W."Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization". Oncology Letters 14.5 (2017): 5400-5408.
Chicago
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q., Ji, W., Zhang, T., Lv, W."Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization". Oncology Letters 14, no. 5 (2017): 5400-5408. https://doi.org/10.3892/ol.2017.6836
Copy and paste a formatted citation
x
Spandidos Publications style
Yan T, Li HY, Wu JS, Niu Q, Duan WH, Han QZ, Ji WM, Zhang T and Lv W: Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization. Oncol Lett 14: 5400-5408, 2017.
APA
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q. ... Lv, W. (2017). Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization. Oncology Letters, 14, 5400-5408. https://doi.org/10.3892/ol.2017.6836
MLA
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q., Ji, W., Zhang, T., Lv, W."Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization". Oncology Letters 14.5 (2017): 5400-5408.
Chicago
Yan, T., Li, H., Wu, J., Niu, Q., Duan, W., Han, Q., Ji, W., Zhang, T., Lv, W."Astaxanthin inhibits gemcitabine‑resistant human pancreatic cancer progression through EMT inhibition and gemcitabine resensitization". Oncology Letters 14, no. 5 (2017): 5400-5408. https://doi.org/10.3892/ol.2017.6836
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