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Original Research

Open Access

PI3K inhibitor promotes tumor vessel normalization and improves treatment outcomes of breast cancer with doxorubicin

  • Baihui Li1,†
  • Yuanyuan Tian1,†
  • Ju Huang1
  • Haiying Zhang1
  • Jiao Zhao1
  • Lihong Zhang1
  • Wei Li1,*,

1The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, 130021 Changchun, Jilin, China

DOI: 10.22514/ejgo.2023.058 Vol.44,Issue 4,August 2023 pp.55-65

Submitted: 10 August 2022 Accepted: 29 November 2022

Published: 15 August 2023

*Corresponding Author(s): Wei Li E-mail: liwei2006@jlu.edu.cn

† These authors contributed equally.

Abstract

HS-173 is a specific inhibitor of the Phosphoinositide 3-Kinase α (PI3Kα) subtype. Although it was shown to potentially inhibit tumor angiogenesis, experimental validation studies are still needed. This study provides an experimental basis for the role of HS-173 in breast cancer. A mouse model of subcutaneous transplantation breast cancer was constructed. The mice were treated with different concentrations of HS-173. Immunohistochemical staining was used to detect tumor microvessel density, and the appropriate concentration was determined. Immunofluorescence was used to detect the morphology integrity of tumor vessels’ lumen, transmission electron microscopy to detect tight junctions between endothelial cells and the integrity of the basement membrane, Doppler ultrasound to detect tumor blood perfusion, and small animal live imaging to detect the penetration of doxorubicin in the tumor tissues. After HS-173 treatment, the number of tumor interstitial microvessels decreased, the lack of tumor vascular lumen was reduced, and the continuity and integrity of the vascular lumen were increased. Vascular endothelial cells showed complete morphology with good tight junctions. The extracellular matrix was rich in components and tended to form basement membranes. HS-173 also increased the blood perfusion in the tumor tissue compared with the doxorubicin treatment alone. Further, the fluorescence signal intensity of the tumor tissue doxorubicin was significantly enhanced after HS-173 treatment. The PI3K inhibitor HS-173 showed promising potential in inhibiting tumor angiogenesis and improving the structure and function of blood vessels in the tumor microenvironment.


Keywords

Tumor blood vessels; Normalization of tumor blood vessels; PI3K inhibitors; Breast cancer


Cite and Share

Baihui Li,Yuanyuan Tian,Ju Huang,Haiying Zhang,Jiao Zhao,Lihong Zhang,Wei Li. PI3K inhibitor promotes tumor vessel normalization and improves treatment outcomes of breast cancer with doxorubicin. European Journal of Gynaecological Oncology. 2023. 44(4);55-65.

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