Enhanced phototoxicity of photodynamic treatment by Cx26‐composed GJIC via ROS‐, calcium‐ and lipid peroxide‐mediated pathways

Wu Deng‐Pan; Lin Tian‐Yu; Bai Li‐Ru; Huang Jin‐Lan; Zhou Yan; Zhou Nan; Zhong Sheng‐Lei; Gao Shan; Yin Xiao‐Xing

摘要

Abstract > In spite of the promising initial treatment responses presented by photodynamic therapy (PDT), 5‐year recurrence rates remain high level. Therefore, improvement in the efficacy of PDT is needed. There are reports showing that connexin(Cx) 26‐composed gap junctional intercellular communication (GJIC) enhances the intercellular propagation of “death signal”, thereby increasing chemotherapeutic cytotoxicity. However, it is unclear whether Cx26‐formed GJIC has an effect on PDT phototoxicity. The results in the present study showed that Cx26‐composed GJ formation at high density enhances the phototoxicity of Photofrin‐PDT. When the Cx26 is not expressed or Cx26 channels are blocked, the phototoxicity in high‐density cultures substantially reduces, indicating that the enhanced PDT phototoxicity at high density is mediated by Cx26‐composed GJIC. The GJIC‐mediated increase in PDT phototoxicity was associated with ROS, calcium and lipid peroxide‐mediated stress signaling pathways. The work presents the ability of Cx26‐composed GJIC to enhance the sensitivity of malignant cells to PDT, and indicates that maintenance or increase of Cx26‐formed GJIC may be a profitable strategy towards the enhancement of PDT therapeutic efficiency. Picture : The survival response of Photofrin‐PDT in Dox‐treated (Cx26 expressing, GJ‐formed) and Dox‐untreated cells (Cx26 non‐expressing, GJ‐unformed) at high‐cell density condition. </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”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 尽管光动力疗法（PDT）提出了有希望的初始治疗响应，但5年的复发率仍保持高水平。因此，需要改善PDT的功效。有报道显示Connexin（CX）26组成的间隙连接细胞间通信（GJIC）增强了“死亡信号”的细胞间繁殖，从而增加了化学治疗性细胞毒性。然而，目前尚不清楚CX26形成的GJIC是否对PDT光毒性作用。本研究中的结果表明，高密度的CX26组合的GJ形成增强了PhotoFrin-PDT的光毒性。当不表达CX26或阻断CX26通道时，高密度培养物中的光毒性基本上降低，表明高密度的增强的PDT光毒性由CX26组成的GJIC介导。 GJIC介导的PDT光毒性的增加与ROS，钙和脂质过氧化物介导的应力信号传导途径有关。该工作介绍了CX26-组合的GJIC以增强恶性细胞对PDT的敏感性的能力，并表明CX26形成的GJIC的维护或增加可能是增强PDT治疗效率的有利可图。图片</ b> ：在高细胞密度条件下，在多尺处理（CX26表达，GJ-形成的）和DOX-未经处理的细胞（CX26非表达，GJ-Unformsed）中的Photofrin-PDT的存活响应。 </ 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-33894/'>《Journal of Biophotonics》</a> <b style="margin: 0 2px;">|</b><span>2017年第12期</span><b style="margin: 0 2px;">|</b><span>共11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=Wu Deng‐Pan&option=202" target="_blank" rel="nofollow">Wu Deng‐Pan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Lin Tian‐Yu&option=202" target="_blank" rel="nofollow">Lin Tian‐Yu;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bai Li‐Ru&option=202" target="_blank" rel="nofollow">Bai Li‐Ru;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Huang Jin‐Lan&option=202" target="_blank" rel="nofollow">Huang Jin‐Lan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhou Yan&option=202" target="_blank" rel="nofollow">Zhou Yan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhou Nan&option=202" target="_blank" rel="nofollow">Zhou Nan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zhong Sheng‐Lei&option=202" target="_blank" rel="nofollow">Zhong Sheng‐Lei;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gao Shan&option=202" target="_blank" rel="nofollow">Gao Shan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yin Xiao‐Xing&option=202" target="_blank" rel="nofollow">Yin Xiao‐Xing;</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>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. China;</p> <p>Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyPharmacy School of Xuzhou Medical UniversityXuzhou City Jiangsu Province 221004 P.R. 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/178.html" title="生物物理学">生物物理学;</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=photodynamic therapy&option=203" rel="nofollow">photodynamic therapy;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Gap junctional intercellular communication&option=203" rel="nofollow">Gap junctional intercellular communication;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Connexin26&option=203" rel="nofollow">Connexin26;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=phototoxicity&option=203" rel="nofollow">phototoxicity;</a> </p> <div class="translation"> 机译：光动力疗法;间隙连接细胞间通信;Connexin26;光毒性; 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<span>机译：一种鉴定参与脂质调节的分子和蛋白质的方法，测试一种物质作为调节脂质水平的治疗剂，治疗脂质介导的疾病和患有脂质介导的疾病的患者，治疗宿主的脂质水平或预防脂质介导的疾病，治疗或预防动脉粥样硬化或与动脉粥样硬化有关的疾病，筛选诊断动脉粥样硬化的遗传易感性或与动脉粥样硬化或脂质介导的疾病有关的疾病，在组织中表达hbm蛋白并调节患者中的脂质水平，确定脂质介导疾病易感性的诊断测定法，用于治疗脂质介导疾病的组合物以及用于治疗患有疾病或脂质介导疾病的患者的联合疗法 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130446859704.html">Compound derived from amine or a pharmacologically acceptable salt thereof, drug, insulin tolerance enhancing agent, blood sugar lowering agent, immunoregulatory agent, aldose reductase inhibiting agent, 5-lipoxygenase inhibiting agent, formation inhibiting agent lipid peroxide, ppar activating agent, antiosteoporosis agent, leukotriene antagonist agent, fat cell promoting agent, cancer cell proliferation inhibiting agent or calcium antagonist agent, pharmaceutical composition and use of a compound</a> <b>[P]</b> . <span> 外国专利：  BR0009594A </span> <span> . 2002-06-04</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：衍生自胺或其药学上可接受的盐的化合物，药物，胰岛素抵抗增强剂，降血糖剂，免疫调节剂，醛糖还原酶抑制剂，5-脂氧合酶抑制剂，形成抑制剂脂质过氧化物，ppar活化剂，抗骨质疏松剂，白三烯拮抗剂，脂肪细胞促进剂，癌细胞增殖抑制剂或钙拮抗剂，药物组合物和化合物的用途 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130412081962.html">a new application of prickly pear flowers and its derivatives in the treatment and prevention of calcium mediated lithiases (57, a lot of people in the world suffer from problems decalculs urinary. these calculations are usually made of decalcium oxalate monohydrate (com) and calcium oxalate dihydrate (ocd).in this study, the crystals of cmo were reconstructed enmu00e9langeant and stirring equal volumes of solutions of calcium oxalate (2ml / 1omm.we also added options to inhibitors of cristauxd'com mixture then evaluates the activity of the inhibitor by the aggregate crystals or crystals in a cell by observing under the light microscope and the mallassez magnification. inhibitors of crystals are obtained by pendant24h com decoction in water.</a> <b>[P]</b> . <span> 外国专利：  MA37725A1 </span> <span> . 2016-07-29</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：刺梨花及其衍生物在治疗和预防钙介导的锂结石中的新应用（57，世界上很多人都患有排尿问题。这些计算通常是由一水合草酸钙和草酸钙组成的。二水合物（OCD）。在这项研究中，将cmo晶体重构为enm u00e9langeant，并搅拌等体积的草酸钙溶液（2ml / lomm）。我们还为cristauxd'com混合物的抑制剂添加了选项，然后评估了通过在光学显微镜下观察和通过Mallassez放大倍数观察细胞中的聚集晶体或晶体，通过在水中悬垂24h煎煮获得晶体抑制剂。 </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> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 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