The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia        <i >in vitroin vitro        and        <i >in vivoin vivo

Zhang Xue‐Hong; Wang Xin‐Yu; Zhou Zhi‐Wei; Bai Hua; Shi Lin; Yang Yin‐Xue; Zhou Shu‐Feng; Zhang Xiao‐Chun

摘要

Abstract > Digoxin is a member of cardiac glycosides and recent studies show that digoxin plays anticancer role in several types of cancer. However, the anticancer effects and mechanism of digoxin in leukemia is largely unknown. Her, our data show that digoxin treatment significantly inhibits leukemia cell viability. In addition, digoxin treatment significantly induced apoptosis and G2/M cell cycle arrest in leukemia cells. Furthermore, we demonstrated that digoxin treatment inactivate that oncogenic pathway Akt/mTOR signaling in leukemia cells. In addition, our data show that digoxin treatment induces activation of unfolded protein response (UPR) signaling in leukemia cells. Interestingly, our in vitro and in vivo experiments show that combination treatment of digoxin and UPR inhibitor can synergistically suppress leukemia growth and induces apoptosis and cell cycle arrest compared to single drug treatment. In summary, our findings indicate that digoxin has potential anticancer effects on leukemia. The combination of digoxin and UPR signaling inhibitor can exerts synergistic anticancer activity against leukemia. ? 2017 BioFactors, 43(6):812–820, 2017 </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“main”> <标题类型=“main”>摘要</标题> > Digoxin是心脏糖苷的成员，最近的研究表明，Digoxin在几种类型的癌症中发挥抗癌作用。然而，白血病中高辛的抗癌效果和机制在很大程度上是未知的。她的数据显示，Digoxin治疗显着抑制白血病细胞活力。此外，Digoxin治疗在白血病细胞中显着诱导细胞凋亡和G2 / M细胞周期停滞。此外，我们证明了地氧蛋白治疗灭活了白血病细胞中的致癌途径akt / mtor信号传导。此外，我们的数据表明，Digoxin治疗诱导白血病细胞中展开蛋白质反应（UPR）信号传导的激活。有趣的是，我们在体外的体外</ i>和实验表明，与单一药物治疗相比，Digoxin和UPR抑制剂的组合治疗可以协同抑制白血病生长并诱导细胞凋亡和细胞循环滞留。总之，我们的研究结果表明，Digoxin对白血病具有潜在的抗癌影响。高辛和UPR信号传导抑制剂的组合可以对白血病产生协同抗癌活性。还2017年生物actors，43（6）：812-820,2017 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-14799/'>《BioFactors》</a> <b style="margin: 0 2px;">|</b><span>2017年第6期</span><b style="margin: 0 2px;">|</b><span>共9页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Xue‐Hong&option=202" target="_blank" rel="nofollow">Zhang Xue‐Hong;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Wang Xin‐Yu&option=202" target="_blank" rel="nofollow">Wang Xin‐Yu;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhou Zhi‐Wei&option=202" target="_blank" rel="nofollow">Zhou Zhi‐Wei;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bai Hua&option=202" target="_blank" rel="nofollow">Bai Hua;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shi Lin&option=202" target="_blank" rel="nofollow">Shi Lin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yang Yin‐Xue&option=202" target="_blank" rel="nofollow">Yang Yin‐Xue;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhou Shu‐Feng&option=202" target="_blank" rel="nofollow">Zhou Shu‐Feng;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhang Xiao‐Chun&option=202" target="_blank" rel="nofollow">Zhang Xiao‐Chun;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of PediatricsGeneral Hospital Ningxia Medical UniversityYinchuan People's Republic of China;</p> <p>Department of Pharmaceutical SciencesCollege of Pharmacy University of South FloridaTampa FL USA;</p> <p>Department of Radiation OncologyUniversity of Texas Southwestern Medical CenterDallas TX USA;</p> <p>Department of PediatricsGeneral Hospital Ningxia Medical UniversityYinchuan People's Republic of China;</p> <p>Department of PediatricsGeneral Hospital Ningxia Medical UniversityYinchuan People's Republic of China;</p> <p>Department of Colorectal SurgeryGeneral Hospital Ningxia Medical UniversityYinchuan People's Republic of China;</p> <p>Department of Pharmaceutical SciencesCollege of Pharmacy University of South FloridaTampa FL USA;</p> <p>Department of PediatricsGeneral Hospital Ningxia Medical UniversityYinchuan People's Republic of China;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/177.html" title="生物化学">生物化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=digoxin&option=203" rel="nofollow">digoxin;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=UPR signaling inhibitor&option=203" rel="nofollow">UPR signaling inhibitor;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=anticancer activity&option=203" rel="nofollow">anticancer activity;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=leukemia&option=203" rel="nofollow">leukemia;</a> </p> <div class="translation"> 机译：地胜;UPR信号抑制剂;抗癌活动;白血病; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-cancer_thesis/0201270490612.html">在体内和体外条件下阿奇霉素通过抑制自噬和上调结肠癌细胞内DR4/5蛋白水平增强TRAIL抗癌活性</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Xinran Qiao&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Xinran Qiao,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Xiaofei Wang&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Xiaofei Wang,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yue Shang&option=202" target="_blank" rel="nofollow" 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王月莉</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=董曼&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,董曼</a> <span> <a href="/journal-cn-6650/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 陕西医学杂志 </a> </span> <span> . 2021</span><span>,第008期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-34926_thesis/020221207863.html">新型铂抗癌药的研究 (Ⅰ)含稳定氮氧自由基结构的铂配合物的合成、结构及初步体外抗癌活性的研究</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=何健&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 何健</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=扬一昆&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,扬一昆</a> <span> <a href="/conference-cn-34926/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国国际生物技术与医药产业学术研讨会 </a> <span> <span> . 1996</span> </span> </div> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/020313620189.html">噻唑烷酮化合物组合在耐药肺癌细胞系中的体内外协同抗癌活性</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李秀娥&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李秀娥</a> <span> . 2010</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/061203291613.html">具有协同抗癌活性的中间体药物和聚乙二醇偶联协同抗癌药物、及其制备方法和应用</a> <b>[P]</b> . <span> 中国专利： CN107670048B </span> <span> . 2019.04.26</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120100796435.html">具有协同抗癌活性的中间体药物和聚乙二醇偶联协同抗癌药物、及其制备方法和应用</a> <b>[P]</b> . <span> 中国专利： CN109843333A </span> <span> . 2019-06-04</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130401701472.html">INTERMEDIATE DRUG WITH SYNERGISTIC ANTICANCER ACTIVITY AND POLYETHYLENE GLYCOL-COUPLED SYNERGISTIC ANTICANCER DRUG, AND PREPARATION METHOD THEREFOR AND USE THEREOF</a> <b>[P]</b> . <span> 外国专利：  US2020261588A1 </span> <span> . 2020-08-20</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：具有增效剂活性的中间药和聚乙二醇偶联增效剂的中间体及其制备方法和用途 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130403574796.html">INTERMEDIATE DRUG WITH SYNERGISTIC ANTICANCER ACTIVITY AND POLYETHYLENE GLYCOL-COUPLED SYNERGISTIC ANTICANCER DRUG, AND PREPARATION METHOD THEREFOR AND USE THEREOF</a> <b>[P]</b> . <span> 外国专利：  WO2019041733A1 </span> <span> . 2019-03-07</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：具有增效剂活性的中间药和聚乙二醇偶联增效剂的中间体及其制备方法和用途 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130422982067.html">compound, pharmaceutical composition, methods for preparing a pharmaceutical composition, for inhibiting raf activity in a cell, in vitro or in vivo, for inhibiting cell proliferation, in vitro or in vivo, and for treating a disease or condition, and, use of a compound</a> <b>[P]</b> . <span> 外国专利：  BRPI0710808A2 </span> <span> . 2012-01-31</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：化合物，药物组合物，制备药物组合物，体外或体内抑制raf活性，体外或体内抑制细胞增殖以及治疗疾病或病症的方法，以及药物的用途复合 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> 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The combination of digoxin and GSK2606414 exerts synergistic anticancer activity against leukemia in vitroin vitro and in vivoin vivo

摘要