{"title":"PI3K inhibitor promotes tumor vessel normalization and improves treatment outcomes of breast cancer with doxorubicin","authors":"","doi":"10.22514/ejgo.2023.058","DOIUrl":null,"url":null,"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.","PeriodicalId":11903,"journal":{"name":"European journal of gynaecological oncology","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of gynaecological oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22514/ejgo.2023.058","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
EJGO is dedicated to publishing editorial articles in the Distinguished Expert Series and original research papers, case reports, letters to the Editor, book reviews, and newsletters. The Journal was founded in 1980 the second gynaecologic oncology hyperspecialization Journal in the world. Its aim is the diffusion of scientific, clinical and practical progress, and knowledge in female neoplastic diseases in an interdisciplinary approach among gynaecologists, oncologists, radiotherapists, surgeons, chemotherapists, pathologists, epidemiologists, and so on.