典型文献
FK228 potentiates topotecan activity against small cell lung cancer cells via induction of SLFN11
文献摘要：
The response rate of topotecan,as a second-line chemotherapeutic drug for small cell lung cancer,is～20％.DNA/RNA helicase SLFN11(schlafen family member 11),a member of the Schlafen(SLFN)family,is a crucial determinant of response to many DNA damaging agents,expression of SLFN11 tends to augment the antitumor effects of the commonly used DNA-targeting agents.In the present study we investigated how SLFN11 expression regulated the sensitivity of small cell lung cancer to topotecan.We showed that SLFN11 expression levels were positively associated with the sensitivity to topotecan in a panel of seven SCLC cell lines.Topotecan treatment induced different patterns of the DNA response network in SCLC cells:DNA damage response(DDR)was more prominently activated in SLFN1 1-deficient SCLC cell line H82 than in SLFN1 1-plentiful SCLC cell line DMS273,whereas topotecan induced significant accumulation of p-Chk1,p-RPA2 and Rad51 in H82 cells,but not in DMS273 cells.We unraveled that SLFN11 expression was highly negatively correlated to the methylation of the SLFN11 promoter.HDAC inhibitors FK228 and SAHA dose-dependently increased SLFN11 expression through suppressing DNA methylation at the SLFN11 promoter,thereby sensitizing SCLC cells to topotecan.Finally,we assessed the methylation status of the SLFN11 promoter in 27 SCLC clinical specimens,and found that most of the clinical samples(24/27)showed DNA methylation at the SLFN11 promoter.In conclusion,it is feasible to combine topotecan with FK228 to improve the response rate of topotecan in SCLC patients.
文献关键词：
中图分类号：
作者姓名：
Yan-ping Yin;Li-ying Ma;Guo-zhen Cao;Jing-han Hua;Xiao-tong Lv;Wen-chu Lin
作者机构：
High Magnetic Field Laboratory,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031,China;University of Science and Technology of China,Hefei 230026,China;Key Laboratory of High Magnetic Field and Ion Beam Physical Biology,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031,China
文献出处：
引用格式：
[1]Yan-ping Yin;Li-ying Ma;Guo-zhen Cao;Jing-han Hua;Xiao-tong Lv;Wen-chu Lin-.FK228 potentiates topotecan activity against small cell lung cancer cells via induction of SLFN11)[J].中国药理学报（英文版）,2022(08):2119-2127
A类：
FK228,topotecan,SLFN11,schlafen,Schlafen,SLFN,SLFN1,H82,DMS273
B类：
potentiates,activity,against,small,lung,cancer,cells,via,induction,response,rate,second,chemotherapeutic,drug,is,helicase,family,member,crucial,determinant,many,damaging,agents,expression,tends,augment,antitumor,effects,commonly,used,targeting,In,present,study,investigated,regulated,sensitivity,We,showed,that,levels,were,positively,associated,panel,seven,SCLC,lines,Topotecan,treatment,induced,different,patterns,network,damage,DDR,was,more,prominently,activated,deficient,than,plentiful,whereas,significant,accumulation,Chk1,RPA2,Rad51,but,not,unraveled,highly,negatively,correlated,methylation,promoter,HDAC,inhibitors,SAHA,dose,dependently,increased,through,suppressing,thereby,sensitizing,Finally,assessed,status,clinical,specimens,found,most,samples,conclusion,feasible,combine,improve,patients
AB值：
0.420561
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
