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

IF 0.5 4区 医学 Q4 OBSTETRICS & GYNECOLOGY European journal of gynaecological oncology Pub Date : 2023-01-01 DOI:10.22514/ejgo.2023.058
{"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.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
PI3K抑制剂促进肿瘤血管正常化,改善阿霉素治疗乳腺癌的效果
HS-173是磷酸肌肽3-激酶α (PI3Kα)亚型的特异性抑制剂。虽然它被证明可能抑制肿瘤血管生成,但仍需要实验验证研究。本研究为HS-173在乳腺癌中的作用提供了实验依据。建立小鼠皮下移植乳腺癌模型。用不同浓度的HS-173处理小鼠。免疫组化染色检测肿瘤微血管密度,确定适宜浓度。采用免疫荧光检测肿瘤血管管腔形态完整性,透射电镜检测内皮细胞与基底膜紧密连接完整性,多普勒超声检测肿瘤血液灌注,小动物活体成像检测阿霉素在肿瘤组织中的渗透情况。HS-173治疗后,肿瘤间质微血管数量减少,肿瘤血管管腔缺失减少,血管管腔连续性和完整性增强。血管内皮细胞形态完整,紧密连接良好。细胞外基质成分丰富,易于形成基底膜。与单独使用阿霉素治疗相比,HS-173也增加了肿瘤组织的血液灌注。此外,HS-173治疗后肿瘤组织的荧光信号强度明显增强。PI3K抑制剂HS-173在抑制肿瘤血管生成、改善肿瘤微环境血管结构和功能方面显示出良好的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
25.00%
发文量
58
审稿时长
1 months
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.
期刊最新文献
Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study. Vulvar cancer in young woman—case report Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature Evaluation of colposcopy and LEEP results performed in gynecology and gynecological oncology surgery services The infrequent large pelvi-perineal tumors as a surgical dilemma: en bloc resection and long-term results
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1