Open Access

Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells

  • Authors:
    • Ying Sun
    • Yunfeng Lian
    • Xue Mei
    • Jinchan Xia
    • Long Feng
    • Jianfeng Gao
    • Huaming Xu
    • Xiaoyan Zhang
    • Huitong Yang
    • Xu Hao
    • Yilin Feng
  • View Affiliations

  • Published online on: September 11, 2024     https://doi.org/10.3892/ijo.2024.5690
  • Article Number: 102
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Macrophages have crucial roles in immune responses and tumor progression, exhibiting diverse phenotypes based on environmental cues. In the present study, the impact of cinobufagin (CB) on macrophage polarization and the consequences on tumor‑associated behaviors were investigated. Morphological transformations of THP‑1 cells into M0, M1 and M2 macrophages were observed, including distinct changes in the size, shape and adherence properties of these cells. CB treatment inhibited the viability of A549 and LLC cells in a concentration‑dependent manner, with an IC50 of 28.8 and 30.12 ng/ml, respectively. CB at concentrations of <30 ng/ml had no impact on the viability of M0 macrophages and lung epithelial (BEAS‑2B) cells. CB influenced the expression of macrophage surface markers, reducing CD206 positivity in M2 macrophages without affecting CD86 expression in M1 macrophages. CB also altered certain expression profiles at the mRNA level, notably downregulating macrophage receptor with collagenous structure (MARCO) expression in M2 macrophages and upregulating tumor necrosis factor‑α and interleukin‑1β in both M0 and M1 macrophages. Furthermore, ELISA analyses revealed that CB increased the levels of pro‑inflammatory cytokines in M1 macrophages and reduced the levels of anti‑inflammatory factors in M2 macrophages. CB treatment also attenuated the migration and invasion capacities of A549 and LLC cells stimulated by M2 macrophage‑conditioned medium. Additionally, CB modulated peroxisome proliferator‑activated receptor γ (PPARγ) and MARCO expression in M2 macrophages and epithelial‑mesenchymal transition in A549 cells, which was partially reversed by rosiglitazone, a PPARγ agonist. Finally, CB and cisplatin treatments hindered tumor growth in vivo, with distinct impacts on animal body weight and macrophage marker expression in tumor tissues. In conclusion, the results of the present study demonstrated that CB exerted complex regulatory effects on macrophage polarization and tumor progression, suggesting its potential as a modulator of the tumor microenvironment and a therapeutic for cancer treatment.
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November-2024
Volume 65 Issue 5

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Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Sun Y, Lian Y, Mei X, Xia J, Feng L, Gao J, Xu H, Zhang X, Yang H, Hao X, Hao X, et al: Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells. Int J Oncol 65: 102, 2024.
APA
Sun, Y., Lian, Y., Mei, X., Xia, J., Feng, L., Gao, J. ... Feng, Y. (2024). Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells. International Journal of Oncology, 65, 102. https://doi.org/10.3892/ijo.2024.5690
MLA
Sun, Y., Lian, Y., Mei, X., Xia, J., Feng, L., Gao, J., Xu, H., Zhang, X., Yang, H., Hao, X., Feng, Y."Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells". International Journal of Oncology 65.5 (2024): 102.
Chicago
Sun, Y., Lian, Y., Mei, X., Xia, J., Feng, L., Gao, J., Xu, H., Zhang, X., Yang, H., Hao, X., Feng, Y."Cinobufagin inhibits M2‑like tumor‑associated macrophage polarization to attenuate the invasion and migration of lung cancer cells". International Journal of Oncology 65, no. 5 (2024): 102. https://doi.org/10.3892/ijo.2024.5690