Open Access

Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway

  • Authors:
    • In-Hye Ham
    • Lei Wang
    • Dagyeong Lee
    • Jongsu Woo
    • Tae Hoon Kim
    • Hye Young Jeong
    • Hye Jeong Oh
    • Kyeong Sook Choi
    • Tae-Min Kim
    • Hoon Hur
  • View Affiliations

  • Published online on: May 26, 2022     https://doi.org/10.3892/ijo.2022.5375
  • Article Number: 85
  • Copyright: © Ham et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines. Secretome analysis revealed that the levels of several secreted proteins, including C‑C motif chemokine ligand 2, C‑X‑C motif chemokine ligand 1, interleukin (IL)‑6 and IL‑8, were increased in the CM from CAFs co‑cultured with cancer cells compared to CM from cancer cells. Western blot analysis revealed that CAFs activated the JAK/STAT3 signaling pathway in cancer cells. The experimental models revealed that curcumin abrogated the CAF‑mediated activation of the JAK/STAT3 signaling pathway in GC cells. In vivo data revealed the synergistic effects of curcumin with 5‑FU treatment in xenograft GC tumors. These data strongly suggest that the suppression of the JAK/STAT3 signaling pathway counteracts the CAF‑induced chemoresistance of GC cells. It is suggested that curcumin may be a suitable natural product which may be used to overcome chemoresistance by inhibiting the CAF‑induced activation of the JAK/STAT3 signaling pathway in GC.
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July-2022
Volume 61 Issue 1

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

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Spandidos Publications style
Ham I, Wang L, Lee D, Woo J, Kim TH, Jeong HY, Oh HJ, Choi KS, Kim T, Hur H, Hur H, et al: Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway. Int J Oncol 61: 85, 2022
APA
Ham, I., Wang, L., Lee, D., Woo, J., Kim, T.H., Jeong, H.Y. ... Hur, H. (2022). Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway. International Journal of Oncology, 61, 85. https://doi.org/10.3892/ijo.2022.5375
MLA
Ham, I., Wang, L., Lee, D., Woo, J., Kim, T. H., Jeong, H. Y., Oh, H. J., Choi, K. S., Kim, T., Hur, H."Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway". International Journal of Oncology 61.1 (2022): 85.
Chicago
Ham, I., Wang, L., Lee, D., Woo, J., Kim, T. H., Jeong, H. Y., Oh, H. J., Choi, K. S., Kim, T., Hur, H."Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway". International Journal of Oncology 61, no. 1 (2022): 85. https://doi.org/10.3892/ijo.2022.5375