7‑Difluoromethyl‑5,4'‑dimethoxygenistein exerts anti‑angiogenic effects on acute promyelocytic leukemia HL‑60 cells by inhibiting the TLR4/NF‑κB signaling pathway

Xiang,Xueping; Li,Lesai; Bo,Pingjuan; Kuang,Ting; Liu,Sujuan; Xie,Xiaolin; Guo,Sihui; Fu,Xiaohua; Zhang,Yong

doi:10.3892/mmr.2020.11029

7‑Difluoromethyl‑5,4'‑dimethoxygenistein exerts anti‑angiogenic effects on acute promyelocytic leukemia HL‑60 cells by inhibiting the TLR4/NF‑κB signaling pathway

Authors:
- Xueping Xiang
- Lesai Li
- Pingjuan Bo
- Ting Kuang
- Sujuan Liu
- Xiaolin Xie
- Sihui Guo
- Xiaohua Fu
- Yong Zhang
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Affiliations: Department of Internal Medicine, Medical College of Hunan Normal University, Changsha, Hunan 410013, P.R. China, Department of Gynecologic Oncology, Hunan Cancer Hospital, Changsha, Hunan 410013, P.R. China
Published online on: March 18, 2020 https://doi.org/10.3892/mmr.2020.11029
Pages: 2251-2259
Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiogenesis plays an important role in the development and metastasis of tumors, and anti-angiogenesis agents are used to treat tumors. For example, the acute promyelocytic leukemia (APL) may be treated with arsenic trioxide. Angiogenesis in APL is a multi‑step dynamic equilibrium process coordinated by various angiogenic stimulators and inhibitors, which play key roles in the occurrence, progression and chemosensitivity of this disease. Our research group previously synthesized 7‑difluoromethyl‑5,4'‑dimethoxygenistein (DFMG), and found that it inhibits angiogenesis during atherosclerotic plaque formation. In the present study, the effect and mechanism of DFMG in angiogenesis induced by APL HL‑60 cells was investigated using a chick embryo chorioallantoic membrane model and Matrigel tubule formation assays. The results obtained revealed an anti‑angiogenesis effect of DFMG towards HL‑60 cells. When the Toll‑like receptor 4/nuclear factor‑κB (TLR4/NF‑κB) signaling pathway was inhibited, the anti‑angiogenic effect of DFMG was further enhanced. However, when the TLR4/NF‑κB signaling pathway was activated, the anti‑angiogenic effect of DFMG was attenuated. These results demonstrated that DFMG inhibits angiogenesis induced by APL HL‑60 cells, and provides insights into the mechanism by which DFMG inhibits the TLR4/NF‑κB signaling pathway. In conclusion, in the present study, the anti‑angiogenesis effect of DFMG on APL has been reported, and the mechanism by which DFMG induced the anti‑angiogenesis effect was explored. These findings have provided a potential new drug candidate for the treatment of patients with APL.

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