期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 185, 期 2, 页码 572-580出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2014.10.017
关键词
-
类别
资金
- Scientific Research from the Ministry of Education, Science, and Culture of Japan [23112501]
- Naito Foundation
- Grants-in-Aid for Scientific Research [26293041, 25670184, 26115701, 26861698, 24390448, 26861540, 15K15726, 26463035, 15K20357, 25462846] Funding Source: KAKEN
Tumor angiogenesis plays an important role in tumor progression and metastasis. Tumor endothelial cells (TECs) are a therapeutic target of antiangiogenic chemotherapy that was recently developed and is currently being investigated in the clinic with promising results. Low-dose chemotherapy, which is the Long-term administration of relatively Low doses of chemotherapeutic agents, has been proposed for targeting tumor angiogenesis in various types of cancers. ALthough the efficacy of low-dose chemotherapy has been confirmed in several clinical models, some studies show insufficienttherapeutic effect for malignant cancers. As a possible mechanism of the treatment failure, it has been considered that tumor cells may acquire resistance to this therapy. However, drug resistance by TECs may also be due to another mechanism for resistance of tumor cells to low-dose chemotherapy. We reported elsewhere that TECs were resistant to the anticancer drug paclitaxel, which is a mitotic inhibitor, concomitant with P-glycoprotein up-regulation. Verapamil, a P-glycoprotein inhibitor, abrogated TEC resistance in vitro. Herein, we demonstrated that verapamil coadministration enhanced the effects of Low-dose paclitaxel concomitant with inhibiting tumor angiogenesis in a preclinical in vivo mouse melanoma xenograft model. Furthermore, verapamil coadministration reduced lung metastasis. These results suggest that inhibiting P-gLycoprotein in TECs may be a novel strategy for low-dose chemotherapy targeting TECs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据