Luteolin inhibits angiogenesis of the M2‑like TAMs via the downregulation of hypoxia inducible factor‑1α and the STAT3 signalling pathway under hypoxia

  • Authors:
    • Binbo Fang
    • Xuehai Chen
    • Minmin Wu
    • Hongru Kong
    • Guanyu Chu
    • Zhenxu Zhou
    • Chunwu Zhang
    • Bicheng Chen
  • View Affiliations

  • Published online on: July 3, 2018     https://doi.org/10.3892/mmr.2018.9250
  • Pages: 2914-2922
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Abstract

The imbalance between angiogenic inducers and inhibitors appears to be a critical factor in tumour pathogenesis. Angiogenesis serves a key role in the occurrence, invasion and metastasis of tumours. Macrophages are a major cellular component of human and rodent tumours, where they are usually termed tumour‑associated macrophages (TAMs). In malignant tumours, TAMs tend to resemble alternatively activated macrophages (M2‑like), promote TA angiogenesis, strengthen tumour migration and invasive abilities, and simultaneously inhibit antitumor immune responses. In our previous study, luteolin, commonly found in a wide variety of plants, had a strong antitumor effect under normoxia; however, it is unknown whether luteolin serves a similar role under hypoxia. In the present study, cobalt chloride (CoCl2) was used to simulate hypoxia. Hypoxia‑inducible factor‑1α (HIF‑1α), which is difficult to detect under normoxic conditions, was significantly increased. Additionally, vascular endothelial growth factor (VEGF) was also significantly increased in response to CoCl2 treatment. Subsequently, luteolin was applied with CoCl2 to examine the effects of luteolin. Luteolin decreased the expression of VEGF and matrix metalloproteinase‑9, which promote angiogenesis. In addition, luteolin also suppressed the activation of HIF‑1 and phosphorylated‑signal transducer and activator of transcription 3 (STAT3) signalling, particularly within the M2‑like TAMs. The results of the present study provide novel evidence that luteolin, under hypoxic conditions, has a strong anticancer effect via the HIF‑1α and STAT3 signalling pathways.
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September-2018
Volume 18 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Fang B, Chen X, Wu M, Kong H, Chu G, Zhou Z, Zhang C and Chen B: Luteolin inhibits angiogenesis of the M2‑like TAMs via the downregulation of hypoxia inducible factor‑1α and the STAT3 signalling pathway under hypoxia. Mol Med Rep 18: 2914-2922, 2018
APA
Fang, B., Chen, X., Wu, M., Kong, H., Chu, G., Zhou, Z. ... Chen, B. (2018). Luteolin inhibits angiogenesis of the M2‑like TAMs via the downregulation of hypoxia inducible factor‑1α and the STAT3 signalling pathway under hypoxia. Molecular Medicine Reports, 18, 2914-2922. https://doi.org/10.3892/mmr.2018.9250
MLA
Fang, B., Chen, X., Wu, M., Kong, H., Chu, G., Zhou, Z., Zhang, C., Chen, B."Luteolin inhibits angiogenesis of the M2‑like TAMs via the downregulation of hypoxia inducible factor‑1α and the STAT3 signalling pathway under hypoxia". Molecular Medicine Reports 18.3 (2018): 2914-2922.
Chicago
Fang, B., Chen, X., Wu, M., Kong, H., Chu, G., Zhou, Z., Zhang, C., Chen, B."Luteolin inhibits angiogenesis of the M2‑like TAMs via the downregulation of hypoxia inducible factor‑1α and the STAT3 signalling pathway under hypoxia". Molecular Medicine Reports 18, no. 3 (2018): 2914-2922. https://doi.org/10.3892/mmr.2018.9250