心脏毒性
体内
医学
地高辛
A549电池
体外
药理学
活力测定
阿霉素
药品
内科学
癌症
癌症研究
肺癌
化学
心力衰竭
化疗
癌细胞
生物
生物化学
生物技术
作者
Yingying Wang,Qian Ma,Shaolu Zhang,Hongyan Liu,Baoquan Zhao,Bo Du,Wei Wang,Peng Lin,Zhe Zhang,Yuxu Zhong,Dexin Kong
标识
DOI:10.3389/fphar.2020.00186
摘要
Digoxin is widely used to treat heart failure. Epidemiological studies suggested it might be used as an anticancer drug or sensitizing agent for cancer therapy. Adriamycin is a well-known anticancer drug, but often causes cardiotoxicity which limits its use. We recently investigated the anticancer effects of digoxin alone or in combination with adriamycin on human non-small cell lung cancer in vitro and in vivo. Digoxin reduced the viability of A549 and H1299 cells in vitro, increased DNA damage by promoting ROS generation and inhibiting both DNA double strand break (DSB) and single strand break (SSB) repair. Combination with adriamycin showed synergistic antiproliferative effects at the ratios of 1/2IC50DIG׃ IC50ADR and IC50DIG ׃ IC50ADR on A549 and H1299 cells, respectively. In vivo, digoxin potently inhibited A549 growth in both zebrafish and nude mouse xenograft model. Co-treatment with adriamycin not only enhanced the antitumor efficacy, but also reduced the cardiotoxicity. Our findings suggest that digoxin has the potential to be applied as an antitumor drug via inhibiting both DNA DSB and SSB repair, and combination with adriamycin for therapy of human non-small cell lung cancer is reasonable.
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