Open Access

Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5‑FU by promoting the SDF‑1/CXCR4/Akt axis

  • Authors:
    • Quan Zhao
    • Yaxin Long
    • Wen Cheng
    • Yingguang Huang
    • Jinyuan Li
    • Yuejin Li
    • Xing Li
    • Xiaodong Guo
    • Yu Li
    • Guosan Li
    • Kunmei Gong
    • Jian Zhang
  • View Affiliations

  • Published online on: April 29, 2022     https://doi.org/10.3892/ijo.2022.5365
  • Article Number: 75
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

5‑Fluorouracil (5‑FU) is the preferred chemotherapeutic drug used in the treatment of colon cancer; however, drug resistance affects its clinical efficacy. Visfatin, an adipokine that promotes tumour development, has the potential to increase resistance to chemotherapy. The present study aimed to verify the effects of visfatin on the sensitivity of colon cancer cells to 5‑FU and to elucidate the potential mechanisms involved. Tissue microarrays (TMAs) were used to analyse visfatin differential expression in normal colon and colon cancer tissues, and the data were further validated in vitro. Cell Counting Kit‑8, clone formation, caspase‑3/7 activity assays, as well as other analyses were used to verify the effects of visfatin on sensitivity to 5‑FU. TMA and correlation analyses were used to predict and verify the correlation between visfatin and stromal cell‑derived factor‑1 (SDF‑1). Rescue experiments and PI3K/Akt inhibitors were used to verify the role of the visfatin/SDF‑1/Akt axis in the sensitivity of colon cancer cells to 5‑FU. Visfatin was found to be highly expressed in colon cancer tissues and cell lines. Moreover, visfatin knockdown increased apoptosis, reduced cell proliferation and enhanced the chemosensitivity of DLD‑1 and SW48 cells to 5‑FU. A positive correlation between visfatin and SDF‑1 was observed, with the knockdown of visfatin enhancing cell sensitivity to 5‑FU chemotherapy by targeting the SDF‑1/C‑X‑C chemokine receptor type 4 (CXCR4) axis. Furthermore, the Akt signalling pathway downstream of SDF‑1/CXCR4 proved to be critical in the decreased sensitisation of colon cancer cells to 5‑FU induced by visfatin. On the whole, the present study demonstrates that visatin can potentially decrease colon cancer cell apoptosis, promote proliferation and decrease colon cancer cell sensitivity to 5‑FU via the visfatin/SDF‑1/Akt axis.
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June-2022
Volume 60 Issue 6

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

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Copy and paste a formatted citation
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Spandidos Publications style
Zhao Q, Long Y, Cheng W, Huang Y, Li J, Li Y, Li X, Guo X, Li Y, Li G, Li G, et al: Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5‑FU by promoting the SDF‑1/CXCR4/Akt axis. Int J Oncol 60: 75, 2022
APA
Zhao, Q., Long, Y., Cheng, W., Huang, Y., Li, J., Li, Y. ... Zhang, J. (2022). Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5‑FU by promoting the SDF‑1/CXCR4/Akt axis. International Journal of Oncology, 60, 75. https://doi.org/10.3892/ijo.2022.5365
MLA
Zhao, Q., Long, Y., Cheng, W., Huang, Y., Li, J., Li, Y., Li, X., Guo, X., Li, Y., Li, G., Gong, K., Zhang, J."Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5‑FU by promoting the SDF‑1/CXCR4/Akt axis". International Journal of Oncology 60.6 (2022): 75.
Chicago
Zhao, Q., Long, Y., Cheng, W., Huang, Y., Li, J., Li, Y., Li, X., Guo, X., Li, Y., Li, G., Gong, K., Zhang, J."Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5‑FU by promoting the SDF‑1/CXCR4/Akt axis". International Journal of Oncology 60, no. 6 (2022): 75. https://doi.org/10.3892/ijo.2022.5365