吉马酮通过FOXO3-FOXM1轴调控甲状腺癌BCPAP细胞的增殖、迁移和化疗耐药  

Germacrone reguates proliferation,migration and chemoresistance of thyroid cancer BCPAP cells through FOXO3-FOXM1 axis

作　　者：王洪涛 马正 单四新 朱坤良 苑留云 WANG Hongtao;MA Zheng;SHAN Sixin;ZHU Kunliang;YUAN Liuyun(Western Pharmacy,Hebei Yiling Hospital,Shijiazhuang 050011,Hebei,China;Department of Pharmacy,Cangzhou Central Hospital,Cangzhou 061000,Hebei,China;Emergency Department,Cangzhou Central Hospital,Cangzhou 061000,Hebei,China)

机构地区：[1]河北以岭医院西药房,河北石家庄050011 [2]沧州市中心医院药学部,河北沧州061000 [3]沧州市中心医院急诊科,河北沧州061000

出　　处：《中国肿瘤生物治疗杂志》2024年第9期871-877,共7页Chinese Journal of Cancer Biotherapy

基　　金：河北省医学科学研究课题计划项目(No.20220384)。

摘　　要：目的:探究吉马酮通过叉头盒蛋白O3(FOXO3)-FOX亚类M1转录因子(FOXM1)信号通路调控人甲状腺癌细胞BCPAP和多柔比星(DOX)耐药BCPAP细胞(BCPAP/DOX)的增殖、迁移和化疗耐药。方法:常规培养BCPAP细胞,用BCPAP细胞构建BCPAP/DOX细胞,用MTT法检测不同浓度吉马酮对BCPAP和BCPAP/DOX细胞增殖的影响。将BCPAP和BCPAP/DOX细胞分为Ctrl组(空白对照)、sh-NC组(转染sh-NC质粒)、低浓度吉马酮组(0.10 mmol/L)、高浓度吉马酮组(0.15 mmol/L)、高浓度吉马酮(0.15 mmol/L)+sh-FOXO3组(转染sh-FOXO3质粒),用转染试剂将sh-NC质粒和sh-FOXO3质粒转至相应的BCPAP和BCPAP/DOX细胞中。用CCK-8法、划痕愈合实验和WB法分别检测各组细胞的增殖、迁移能力,以及FOXO3、FOXM1、BAX、MMP-9和多药耐药-1(MDR-1)蛋白的表达。结果:在BCPAP和BCPAP/DOX细胞中成功地敲减了FOXO3的表达,低浓度和高浓度吉马酮均可显著抑制BCPAP和BCPAP/DOX细胞的增殖、迁移能力,降低细胞中FOMX1、MMP-9或MDR-1(BCPAP/DOX细胞)蛋白的表达,提升FOXO3和BAX蛋白的表达(均P<0.05),与低浓度比较,高浓度吉马酮的作用更为显著(均P<0.05),敲减FOXO3后可部分逆转吉马酮对这两种细胞的作用(均P<0.05)。结论:吉马酮可能通过FOXO3/FOXM1信号通路调控BCPAP和BCPAP/DOX细胞的增殖和迁移能力,降低BCPAP/DOX细胞化疗耐药性。Objective:To explore how germacrone regulates the proliferation,migration and chemoresistance of human thyroid cancer BCPAP cells and doxorubicin(DOX)resistant BCPAP cells(BCPAP/DOX)through the forkhead box O3(FOXO3)-FOX subclass M1 transcription factor(FOXM1)signaling pathway.Methods:BCPAP cells were cultured routinely and used to construct BCPAP/DOX cells.MTT method was applied to detect the effects of different concentrations of germacrone on the proliferation of BCPAP and BCPAP/DOX cells.BCPAP and BCPAP/DOX cells were divided into control group(Ctrl),negative control group(NC,transfected with sh-NC plasmid),low concentration germacrone group(0.10 mmol/L),high concentration germacrone group(0.15 mmol/L),high concentration germacrone(0.15 mmol/L)+sh-FOXO3 group(transfected with sh-FOXO3 plasmid).The sh-NC plasmid and sh-FOXO3 plasmid were transfected into the corresponding BCPAP and BCPAP/DOX cells with transfection reagents.The proliferation and migration of the cells were detected using CCK-8 assay and scratching healing assay,and the expression of FOXO3,FOXM1,BAX,MMP-9 and multi-drug resistant-1(MDR-1)was detected using WB assay.Results:The expression of FOXO3 was successfully knocked down in BCPAP and BCPAP/DOX cells.Both low and high concentrations of germacrone could significantly inhibit the proliferation and migration of BCPAP and BCPAP/DOX cells,reduce the protein expression of FOMX1,MMP-9 or MDR-1(in BCPAP/DOX cells),and increase the protein expression of FOXO3 and BAX(all P<0.05).Notably,the effects were more significant with high concentration germacrone compared to that of low concentration(all P<0.05).Knockdown of FOXO3 partially reversed the effects of germacrone on these cells(all P<0.05).Conclusion:Germacrone may regulate the proliferation and migration of BCPAP and BCPAP/DOX cells and reduce chemotherapy resistance of BCPAP/DOX cells through the FOXO3/FOXM1 signaling pathway.

关 键 词：吉马酮 叉头盒蛋白O3 叉头盒亚类M1转录因子 甲状腺癌 增殖 迁移 化疗耐药 

分 类 号：R736.1[医药卫生—肿瘤]