和厚朴酚调控FOXM1表达对口腔鳞状细胞癌顺铂耐药的影响  

Influence of honokiol on cisplatin resistance in oral squamous cell carcinoma by regulating FOXM1 expression

作　　者：李琰[1] 赵洪波 张宇涛 LI Yan;ZHAO Hong-bo;ZHANG Yu-tao(Department of Stomatology,Fenyang College,ShanxiMedical University,Fenyang 032200,Shanxi Province,China;Department of Stomatology,Fenyang Hospital of Shanxi Province,Fenyang 032200 Shanxi Province,China)

机构地区：[1]山西医科大学汾阳学院口腔教研室,山西汾阳032200 [2]山西省汾阳医院口腔科,山西汾阳032200

出　　处：《中国临床药理学杂志》2023年第23期3414-3418,共5页The Chinese Journal of Clinical Pharmacology

基　　金：山西省高等学校大学生创新创业训练计划基金资助项目(20221581)。

摘　　要：目的 研究和厚朴酚调控叉头盒蛋白M1(FOXM1)表达对口腔鳞状细胞癌(OSCC)顺铂耐药的影响。方法 用药物浓度递增法建立顺铂耐药细胞株CAL27/DDP。将CAL27/DDP细胞随机分为对照组(正常培养)、模型组(4μmol·L^(-1)顺铂)、和厚朴酚组(20μmol·L^(-1)和厚朴酚+4μmol·L^(-1)顺铂)、和厚朴酚+空载组(20μmol·L^(-1)和厚朴酚+4μmol·L^(-1)顺铂+转染空载质粒)、和厚朴酚+FOXM1过表达组(20μmol·L^(-1)和厚朴酚+4μmol·L^(-1)顺铂+转染FOXM1过表达质粒)。以CCK-8法检测细胞增殖情况,以流式细胞实验检测细胞凋亡情况,以实时荧光定量聚合酶链反应(qRT-PCR)实验检测细胞FOXM1、多药耐药(MDR1) mRNA表达水平,以蛋白质印迹法检测细胞FOXM1、P-糖蛋白(P-gp)表达水平。结果 对照组、模型组、和厚朴酚组、和厚朴酚+空载组、和厚朴酚+FOXM1过表达组的细胞增殖率分别为(100.00±0.00)%、(90.13±17.95)%、(43.69±6.11)%、(45.01±7.23)%和(83.94±15.72)%,细胞凋亡率分别为(3.71±0.85)%、(5.03±1.13)%、(60.12±8.64)%、(61.50±7.96)%和(6.62±0.87)%,FOXM1 mRNA相对表达水平分别为0.99±0.14、0.98±0.19、0.39±0.04、0.37±0.05和0.90±0.17,MDR1 mRNA相对表达水平分别为0.98±0.16、0.99±0.17、0.47±0.08、0.48±0.05和0.91±0.20,FOXM1蛋白相对表达水平分别为1.01±0.20、1.04±0.19、0.60±0.08、0.58±0.06和0.95±0.16,P-gp蛋白相对表达水平分别为0.90±0.21、0.93±0.15、0.49±0.06、0.47±0.09和0.85±0.17。和厚朴酚组的上述指标与对照组、模型组、和厚朴酚+FOXM1过表达组比较,差异均有统计学意义(均P<0.05)。结论 和厚朴酚可抑制FOXM1及耐药基因表达,增强人OSCC顺铂耐药细胞株的顺铂敏感性,减弱其耐药性。Objective To study the influence of honokiol on cisplatin resistance in oral squamous cell carcinoma(OSCC)by regulating the expression of forkhead box protein M1(FOXM1).Methods Cisplatin-resistant cell line CAL27/DDP was established by increasing drug concentration.CAL27/DDP cells were randomly divided into control group(normal culture),model group(4μmol·L^(-1)cisplatin treatment),honokiol group(20μmol·L^(-1)honokiol combined with 4μmol·L^(-1)cisplatin treatment),honokiol+empty group(20μmol·L^(-1)and honokiol combined with 4μmol·L^(-1)cisplatin transfected no-load plasmid simultaneously),honokiol+FOXM1overexpression group(20μmol·L^(-1)honokiol combined with 4μmol·L^(-1)cisplatin were simultaneously transfected with FOXM1 overexpression plasmid).The cell proliferation was detected by cell counting kit-8 method;the apoptosis was detected by flow cytometry;the mRNA expressions of FOXM1 and multidrug resistance 1(MDR1)in cells were detected by quantitative real-time fluorescence quantitative polymerase chain reaction(qRT-PCR);the expressions of FOXM1 and P-glycoprotein(P-gp)Were detected by western blot.Results The cell proliferation rates of control group,model group,honokiol group,honokiol+empty group and honokiol+FOXM1 overexpression group were(100.00±0.00)%,(90.13±17.95)%,(43.69±6.11)%,(45.01±7.23)%and(83.94±15.72)%,respectively;the apoptosis rates were(3.71±0.85)%,(5.03±1.13)%,(60.12±8.64)%,(61.50±7.96)%and(6.62±0.87)%,respectively;the relative expression levels of FOXM1 mRNA were 0.99±0.14,0.98±0.19,0.39±0.04,0.37±0.05 and 0.90±0.17,respectively;the relative expression levels of MDR1 mRNA were0.98±0.16,0.99±0.17,0.47±0.08,0.48±0.05 and 0.91±0.20,respectively;the relative expression levels of FOXM1 protein were 1.01±0.20,1.04±0.19,0.60±0.08,0.58±0.06 and 0.95±0.16,respectively;the relative expression levels of P-gp protein were 0.90±0.21,0.93±0.15,0.49±0.06,0.47±0.09 and 0.85±0.17,respectively.There were statistically significant differences between honokiol group and

关 键 词：和厚朴酚 叉头盒蛋白M1 口腔鳞状细胞癌 顺铂 耐药 

分 类 号：R28[医药卫生—中药学]