摘要
目的探究佛手柑内酯(Bg)对结肠癌细胞5-氟尿嘧啶(5-Fu)耐药性的影响及其机制。方法采用Bg作用人结肠癌SW1116/5-Fu和LoVo/5-Fu耐药细胞系;CCK-8法检测细胞增殖能力;Western blot检测Bcl-2、Bax、EB病毒诱导基因3(EBI3)、STAT3、磷酸化STAT3(p-STAT3)、CYP1B1和MEKK2蛋白质表达。结果Bg作用SW1116、SW1116/5-Fu、LoVo和LoVo/5-Fu细胞后,5-Fu作用细胞的半抑制浓度(IC50)值明显降低(P<0.05),尤其是Bg联合EBI3阻断剂作用细胞后,IC50值明显下降(P<0.05)。Western blot检测结果显示,Bg作用下SW1116/5-Fu和LoVo/5-Fu细胞Bcl-2、EBI3、STAT3、p-STAT3、CYP1B1和MEKK2蛋白质表达水平均明显降低,Bax蛋白质表达水平明显升高。结论Bg可能通过诱导细胞凋亡、抑制EBI3/STAT3信号通路及抑制耐药相关蛋白质CYP1B1和MEKK2表达增强结肠癌细胞对5-Fu的化疗敏感性。
Objective To explore the effect of bergapten(Bg)on resistance to 5-Fluorouracil(5-Fu)in colorectal cancer cell lines,and analyse its mechanism.Methods The human colorectal cancer cell lines SW1116/5-Fu and LoVo/5-Fu resistant cell lines were treated with Bg.Cell proliferation ability was detected by using CCK-8.Western blot was used to detect Bcl-2,Bax,EBI3,STAT3,phosphorylated-STAT3(p-STAT3),CYP1B1 and MEKK2 protein expression.Results The half-inhibitory concentration(IC50)value of 5-Fu in SW1116,SW1116/5-Fu,LoVo and LoVo/5-Fu cells were significantly decreased after treated with Bg,especially after Bg combined with EBI3 acted on cells,the IC50 value decreased significantly(P<0.05).The results of Western blot showed that the expression levels of Bcl-2,EBI3,STAT3,p-STAT3,CYP1B1 and MEKK2 were significantly decreased,while the expression levels of Bax were significantly increased in SW1116/5-Fu and LoVo/5-Fu cells,after treated with Bg.Conclusion Bg may enhance the chemotherapy sensitivity of colorectal cancer cells to 5-Fu via inducing apoptosis,inhibiting the EBI3/STAT3 signaling pathway,and inhibiting the expression of drug resistance-related proteins CYP1B1 and MEKK2.
作者
梁艳芳
叶子瑜
马燕
陈灿
林碧华
曾今诚
LIANG Yanfang;YE Ziyu;MA Yan;CHEN Can;LIN Bihua;ZENG Jincheng(Department of Pathology,Dongguan Hospital Affiliated to Jinan University/Marina Bay Central Hospital of Dongguan,Dongguan,Guangdong 523905,China;Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research,Guangdong Medical University,Dongguan,Guangdong 523808,China;Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,Guangdong Medical University,Dongguan,Guangdong 523808,China)
出处
《重庆医学》
CAS
2020年第14期2255-2259,共5页
Chongqing medicine
基金
广东省基础与应用基础研究基金联合基金(粤莞)项目(2019A1515110042)
广东省医学科研基金项目(A2018123)
东莞市社会科技发展(一般)项目(2018507150251294)。
关键词
结肠肿瘤
佛手柑内酯
氟尿嘧啶
抗药性
肿瘤
EB病毒诱导基因3
colonic neoplasms
bergapten
fluorouracil
drug resistance,neoplasm
epstein-barr virus-inducible gene 3
