Borneol and Tetrandrine Modulate the Blood–Brain Barrier and Blood–Tumor Barrier to Improve the Therapeutic Efficacy of 5-Fluorouracil in Brain Metastasis

Author:

Lin Jui-Feng12,Liu Yen-Shuo3,Huang Yu-Chuen45,Chi Chih-Wen3,Tsai Cheng-Chia6,Tsai Tung-Hu2,Chen Yu-Jen2478ORCID

Affiliation:

1. Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan

2. Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3. Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan

4. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

5. School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan

6. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

7. Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan

8. Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan

Abstract

The efficacy of chemotherapeutic drugs for the treatment of brain metastasis may be compromised by the blood–brain barrier (BBB) and blood–tumor barrier (BTB). P-glycoprotein (P-gp) is a multidrug resistance protein that potentially limits the penetration of chemotherapeutics through the BBB and BTB. 5-Fluorouracil (5-FU) is widely used to treat cancer. Bioactive constituents of medicinal herbs, such as borneol and tetrandrine, potentially improve drug penetration through the BBB and BTB. We hypothesized that borneol and tetrandrine might modulate the BBB and BTB to enhance 5-FU penetration into the brain. To investigate this, in vitro and in vivo models were developed to explore the modulatory effects of borneol and tetrandrine on 5-FU penetration through the BBB and BTB. In the in vitro models, barrier integrity, cell viability, barrier penetration, P-gp activity, and NF-κB expression were assessed. In the in vivo brain metastasis models, cancer cells were injected into the internal carotid artery to evaluate tumor growth. The experimental results demonstrated that borneol and borneol + tetrandrine reduced BBB integrity. The efflux pump function of P-gp was partially inhibited by tetrandrine and borneol + tetrandrine. In the in vivo experiment, borneol + tetrandrine effectively prolonged survival without compromising body weight. In conclusion, BBB and BTB integrity was modulated by borneol and borneol + tetrandrine. The combination of borneol and tetrandrine could be used to improve the chemotherapeutic control of brain metastasis.

Funder

Mackay Memorial Hospital

Publisher

SAGE Publications

Subject

Complementary and alternative medicine,Oncology

全球学者库

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"全球学者库"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前全球学者库共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2023 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3