Open Access

Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype

  • Authors:
    • Jianfeng Ji
    • Yuqin Ding
    • Yue Kong
    • Min Fang
    • Xiaofu Yu
    • Xiaojing Lai
    • Qing Gu
  • View Affiliations

  • Published online on: August 3, 2023     https://doi.org/10.3892/etm.2023.12147
  • Article Number: 448
  • Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study aimed to investigate the aggressive behavior of triple‑negative breast cancer (TNBC) cells that had survived ionizing radiation and explore the potential targets of TNBC combination treatment. Consistent with the previous literature, Axl was highly expressed in TNBC and closely associated with the degree of malignancy based on immunohistochemical staining. Using a gradient irradiation method, the ionizing radiation‑resistant mouse TNBC cell line 4T‑1/IRR was established. It was found that Axl expression was upregulated in 4T‑1/IRR cells. After irradiation by X‑ray, the cell viability and colony formation ability of 4T‑1/IRR cells were significantly increased when compared with the 4T‑1 cells. Combined radiotherapy with Axl inhibition by treatment with R428 and small interfering RNA lentivirus targeting Axl infection significantly reduced cell viability, colony formation ability, DNA double‑stranded break repair, and the invasive and migratory ability of 4T‑1/IRR cells. In vivo, the small animal radiation research platform was applied to precisely administer radiotherapy of the tumor‑bearing mice. R428 treatment combined with 6 Gy X‑ray significantly inhibited the growth of 4T‑1/IRR cells‑derived xenograft tumors in the BALB/c mouse. The results of western blotting showed that the critical molecular mechanism involved in the radioresistance of TNBC cells was the PI3K/Akt/mTOR signaling pathway induced by Axl activation. Thus, it is hypothesized that targeted Axl therapy combined with radiotherapy may have significant potential for the treatment of TNBC.
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September-2023
Volume 26 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Ji J, Ding Y, Kong Y, Fang M, Yu X, Lai X and Gu Q: Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype. Exp Ther Med 26: 448, 2023
APA
Ji, J., Ding, Y., Kong, Y., Fang, M., Yu, X., Lai, X., & Gu, Q. (2023). Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype. Experimental and Therapeutic Medicine, 26, 448. https://doi.org/10.3892/etm.2023.12147
MLA
Ji, J., Ding, Y., Kong, Y., Fang, M., Yu, X., Lai, X., Gu, Q."Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype". Experimental and Therapeutic Medicine 26.3 (2023): 448.
Chicago
Ji, J., Ding, Y., Kong, Y., Fang, M., Yu, X., Lai, X., Gu, Q."Triple‑negative breast cancer cells that survive ionizing radiation exhibit an Axl‑dependent aggressive radioresistant phenotype". Experimental and Therapeutic Medicine 26, no. 3 (2023): 448. https://doi.org/10.3892/etm.2023.12147