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25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway

  • Authors:
    • Saisai Wang
    • Yuanyuan Yao
    • Chunhui Rao
    • Gang Zheng
    • Wenbin Chen
  • View Affiliations / Copyright

    Affiliations: Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China, Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 966-980
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    Published online on: January 11, 2019
       https://doi.org/10.3892/ijo.2019.4684
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Abstract

Hyperlipidemia is associated with metastasis in patients with gastric cancer (GC). 25‑Hydroxycholesterol (25‑HC) is a type of oxysterol which is synthesized from cholesterol and is involved in a number of processes, including inflammation, immune responses and cancer development. However, the role of 25‑HC in gastric cancer remains unknown. In the present study, we demonstrated that 25‑HC had no effects on GC cell proliferation and apoptosis, whereas it decreased the sensitivity of GC cells to 5‑fluorouracil (5‑FU), as demonstrated by the increased cell proliferation and the decreased cell apoptosis. On the other hand, exposure to 2.5‑10 µM of 25‑HC significantly promoted GC invasion, both in vitro (using AGS and MGC‑803 GC cell lines) and in vivo (in an animal model), accompanied by the upregulation of the expression levels of matrix metalloproteinases (MMPs). Further investigations revealed that the promotion of GC invasion was, at least in part due to the activation of Toll‑like receptor 2 (TLR2)/nuclear factor (NF)‑κB signaling. Our results demonstrated that 25‑HC promoted GC cells invasion by upregulating TLR2/NF‑κB‑mediated MMP expression. Thus, on the whole, the findings of this study suggest a novel mechanism of hyperlipidemia‑induced GC progression.
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Copy and paste a formatted citation
Spandidos Publications style
Wang S, Yao Y, Rao C, Zheng G and Chen W: 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. Int J Oncol 54: 966-980, 2019.
APA
Wang, S., Yao, Y., Rao, C., Zheng, G., & Chen, W. (2019). 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. International Journal of Oncology, 54, 966-980. https://doi.org/10.3892/ijo.2019.4684
MLA
Wang, S., Yao, Y., Rao, C., Zheng, G., Chen, W."25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway". International Journal of Oncology 54.3 (2019): 966-980.
Chicago
Wang, S., Yao, Y., Rao, C., Zheng, G., Chen, W."25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway". International Journal of Oncology 54, no. 3 (2019): 966-980. https://doi.org/10.3892/ijo.2019.4684
Copy and paste a formatted citation
x
Spandidos Publications style
Wang S, Yao Y, Rao C, Zheng G and Chen W: 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. Int J Oncol 54: 966-980, 2019.
APA
Wang, S., Yao, Y., Rao, C., Zheng, G., & Chen, W. (2019). 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. International Journal of Oncology, 54, 966-980. https://doi.org/10.3892/ijo.2019.4684
MLA
Wang, S., Yao, Y., Rao, C., Zheng, G., Chen, W."25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway". International Journal of Oncology 54.3 (2019): 966-980.
Chicago
Wang, S., Yao, Y., Rao, C., Zheng, G., Chen, W."25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway". International Journal of Oncology 54, no. 3 (2019): 966-980. https://doi.org/10.3892/ijo.2019.4684
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