文献类型：期刊文献

中文题名：肺癌微环境对骨髓间充质干细胞自发衰老的抑制作用及其调控机制

英文题名：The Inhibitory Effect of Lung Cancer Microenvironment on Self Senescence of BM-MSCs and Its Mechanism

作者：高卓越[1];何建新[1];刘永琦[1,2];卢志伟[1];伍志伟[1,2];骆亚莉[1];张利英[1];苏韫[1];薛娜[1]

第一作者：高卓越

机构：[1]甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,兰州730000;[2]敦煌医学与转化省部共建教育部重点实验室,兰州730000

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

年份：2015

卷号：37

期号：12

起止页码：1646

中文期刊名：中国细胞生物学学报

外文期刊名：Chinese Journal of Cell Biology

收录：CSTPCD;;CSCD:【CSCD2015_2016】；

基金：甘肃省杰出青年基金(批准号:1308RJDA008);国家自然科学基金(批准号:81360588)资助的课题~~

语种：中文

中文关键词：骨髓间充质干细胞;肺癌微环境;衰老;端粒酶;STAT3

外文关键词：bone marrow-derived mesenchymal stem cells; lung cancer microenvironment; senescence; te-lomerase; STAT3

摘要：该文探讨了肺癌微环境对骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells,BM-MSCs)自发衰老的影响及其机制研究。采用Transwell小室建立BM-MSCs与肺腺癌细胞A549非接触共培养体系,通过观察细胞形态学、细胞增殖和细胞衰老等变化以探讨肺腺癌微环境对BM-MSCs自发衰老的影响。利用qPCR技术检测细胞衰老相关端粒酶mRNA水平变化,Western blot技术寻找影响BM-MSCs自发衰老的胞内信号通路.结果显示,共培养7 d后,随着传代代次的增加,共培养组骨髓间充质干细胞(Co-MSCs)细胞形态逐渐由成纤维样漩涡状生长分化为纺锤样集落状生长,细胞增殖速度逐渐增快。同时,与BM-MSCs相比,Co-MSCs没有出现明显的衰老特征,Co-MSCs内端粒酶活性始终处于较低水平,统计学差异显著(P<0.01)。Western blot结果显示,随着传代次数的增加,BM-MSCs的信号转导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)及其磷酸化水平始终处于较低水平,而Co-MSCs的较高,且有逐渐上升的趋势,具有显著差异(P<0.05)。结果表明,肺腺癌微环境诱导Co-MSCs向着永生化细胞方向分化,有助于CoMSCs逃脱衰老,而这可能通过STAT3信号通路的持续活化来调控。
This work was aimed at exploring the inhibition and regulating mechanism of lung cancer mi- croenvironment on self senescence of bone marrow-derived mesenchymal stem cells （BM-MSCs）. It was set up Transwell system in which BM-MSCs were co-cultured with A549 in an indirect way, to study the influence of lung cancer mieroenvironment on self senescence of BM-MSCs by cell morphology, cell proliferation assay and cell senescence dyeing experiment. Meanwhile, it was also studied the regulating mechanism of lung cancer microenviron- ment on BM-MSCs senescence by detecting telomerase mRNA level with qPCR and searching relating signaling pathways with Western blot technology, resnectivelv. Ourresults of 7-days co-cultured indicated that, morphology ofco-cultured bone marrow-derived mesenchymal stem cells （Co-MSCs） greatly turned to spindle-like shape from fi- broblast-like shape. Meanwhile, the whirlpool-like spreading were replaced by colony-like spreading of Co-MSCs. Proliferation of Co-MSCs was increased as cells passaging. Meanwhile, senescence character in Co-MSCs was de- creased compared with that in BM-MSCs as cells passaging. Further study showed that telomerase mRNA level in Co-MSCs was in lower, compared with that in BM-MSCs. It was significant difference statistically （P〈0.01）. The result of Western blot analysis showed that, as cells were passaged, the STAT3 proein and its phosphorylation levels in BM-MSCs were always lower than that in Co-MSCs, and Co-MSCs shown that higher gradually. It was signifi- cant difference statistically （P〈0.05）. Our results suggested that lung cancer microenvironment could induce BM- MSCs differentiate towards immortal cells to help BM-MSCs escape from senescence. The underlying mechanism could be involved in the activation of STAT3 in Co-MSCs.