[1]马梦娇,金冬,张广芹,等.一种新的咪唑通过AMPK/mTOR途径诱导肿瘤细胞自噬[J].南京师范大学学报(自然科学版),2020,43(01):115-121.[doi:10.3969/j.issn.1001-4616.2020.01.017]
 MaMengjiao,JinDong,ZhangGuangqin,et al.ANewKindofImidazolesInducesTumorCellAutophagyviaAMPK/mTORPathway[J].JournalofNanjingNormalUniversity(NaturalScienceEdition),2020,43(01):115-121.[doi:10.3969/j.issn.1001-4616.2020.01.017]
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一种新的咪唑通过AMPK/mTOR途径诱导肿瘤细胞自噬()
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《南京师范大学学报》(自然科学版)[ISSN:1001-4616/CN:32-1239/N]

卷:
第43卷
期数:
2020年01期
页码:
115-121
栏目:
·生物学·
出版日期:
2020-03-15

文章信息/Info

Title:
ANewKindofImidazolesInducesTumorCellAutophagyviaAMPK/mTORPathway
文章编号:
1001-4616(2020)01-0115-07
作者:
马梦娇金冬张广芹于晓璐温传俊
南京师范大学生命科学学院,分子细胞生物学研究所,江苏南京210023
Author(s):
MaMengjiaoJinDongZhangGuangqinYuXiaoluWenChuanjun
SchoolofLifeSciences,NanjingNormalUniversity,InstituteofMolecularandCellBiology,Nanjing210023,China
关键词:
NO.143自噬肿瘤LC3BAMPK/mTOR
Keywords:
NO.143autophagytumorLC3BAMPK/mTOR
分类号:
Q291
DOI:
10.3969/j.issn.1001-4616.2020.01.017
文献标志码:
A
摘要:
自噬与肿瘤的发生有着密切的关系.通过防止受损蛋白质和细胞器的毒性积累,自噬限制氧化应激、慢性组织损伤和致癌信号传导,抑制癌症的发生,这表明了自噬激活在癌症预防和治疗中的作用.研究发现一种新的咪唑,命名为NO.143.利用胰腺癌细胞PANC-1为模型,用MTS检测不同浓度NO.143对细胞活力的影响,共聚焦显微镜观察自噬荧光点,Westernblot检测自噬相关蛋白LC3B、ATG13、p62的表达情况,以及AMPK/mTOR信号通路相关蛋白的表达情况.结果表明,NO.143呈现浓度依赖性地抑制肿瘤细胞的增殖.NO.143能够明显增加细胞中自噬荧光斑点、LC3B表达、ATG13的含量和p62的降解,表明NO.143能够显著上调肿瘤细胞的自噬.进一步研究显示,NO.143能够增加AMPKα的磷酸化水平,降低哺乳动物雷帕霉素靶蛋白(mTOR)和S6的磷酸化水平.相反的,在抑制AMPKα活性后,这种现象发生逆转.这些结果都可能表明NO.143通过AMPK/mTOR信号传导途径诱导肿瘤自噬,抑制肿瘤细胞的增殖.
Abstract:
Autophagyiscloselyrelatedtothetumoroccurrence.Bypreventingtheaccumulationoftoxicitiesindamagedproteinsandorganelles,autophagylimitsoxidativestress,chronictissuedamageandoncogenicsignaling,inhibitingthedevelopmentofcancer.Thisindicatestheroleofautophagyactivationincancerpreventionandtreatment.ItwasfoundanewimidazolenamedNO.143.PANC-1wasusedasamodeltodetecttheeffectofdifferentconcentrationsofNO.143oncellviabilitybyMTS.Theautophagyfluorescencespotswereobservedbyconfocalmicroscopy.Westernblotwasusedtodetecttheexpressionofautophagy-relatedproteinsLC3B,ATG13,p62andtheexpressionofAMPK/mTORsignalingpathway-relatedproteins.TheresultsshowedthatNO.143showedaconcentration-dependentinhibitionoftumorcellproliferation.NO.143cansignificantlyincreaseautophagicfluorescentspotsincells,increaseLC3Bexpression,ATG13contentandp62degradation.TheseresultsshowthatNO.143cansignificantlyup-regulateautophagyintumorcells.FurtherstudiesshowedthatNO.143wasabletoincreasethephosphorylationlevelofAMPKαandreducethephosphorylationlevelsofmammalianrapamycintargetprotein(mTOR)andS6.Conversely,thisphenomenonreversesafterinhibitingAMPKαactivity.TheseresultsmayindicatethatNO.143inducestumorautophagythroughtheAMPK/mTORsignalingpathwayandinhibitstumorcellproliferation.

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备注/Memo

备注/Memo:
收稿日期:2019-06-09.
基金项目:国家自然科学基金项目(2012104GZ30057).
通讯作者:温传俊,副教授,研究方向:肿瘤分子细胞生物学.E-mail:wenchuanjun@hotmail.com
更新日期/Last Update: 2020-03-15