机构地区:[1]山西医科大学第一临床医学院,山西太原030000 [2]山西医科大学第一医院药物临床试验机构,山西太原030000
出 处:《中国临床药理学杂志》2024年第20期3013-3017,共5页The Chinese Journal of Clinical Pharmacology
摘 要:目的探究半枝莲种素调控肺鳞癌发生和转移的分子机制。方法用实时荧光定量聚合酶链反应(qRT-PCR)检测不同细胞系中目标基因的相对表达水平。动物实验:将动物随机分成2组,半枝莲种素动物组每天灌胃给予50 mg·kg^(-1)半枝莲种素溶液,模型组每天灌胃给予等体积的0.9%NaCl,测量肿瘤体积。细胞实验:将细胞分为对照组(不做处理)、半枝莲种素组(3.0 g·L^(-1)半枝莲种素)、半枝莲种素+oe-HOXA11-AS组(3.0 g·L^(-1)半枝莲提取物处理并转染HOXA11-AS)、半枝莲种素+oe-HOXA11-AS+XAV939组(3.0 g·L^(-1)半枝莲提取物处理,转染HOXA11-AS并加入10μmol·L^(-1)XAV939)。用5-乙炔基-2’-脱氧尿苷(Edu)和末端转移酶介导的dUTP末端标记法(TUNEL)实验分别检测细胞的增殖率和凋亡率,用Transwell实验检测各组人肺鳞癌细胞NCI-H520的迁移。结果各肺癌细胞系中HOXA11-AS相对表达水平相比正常肺上皮细胞均显著增多(均P<0.05)。35 d时模型组和半枝莲种素动物组肿瘤体积分别为(937.83±67.40)和(512.32±45.61)mm^(3),2组比较,在统计学上差异有统计学意义(P<0.001)。对照组、半枝莲种素组、半枝莲种素+oe-HOXA11-AS组和半枝莲种素+oe-HOXA11-AS+XAV939组细胞迁移数目分别为(127.26±8.92)、(23.76±3.31)、(131.28±9.49)和(27.69±3.57)个,增殖率分别为(56.27±7.49)%、(28.68±4.33)%、(50.12±7.86)%和(13.62±3.54)%,凋亡率分别为(10.86±2.97)%、(43.23±6.78)%、(30.92±4.53)%和(41.77±7.02)%,半枝莲种素组的上述指标与对照组比较,半枝莲种素+oe-HOXA11-AS组的上述指标与半枝莲种素组比较,枝莲种素+oe-HOXA11-AS+XAV939组的上述指标与半枝莲种素+oe-HOXA11-AS组比较,在统计学上差异均有统计学意义(P<0.05,P<0.01,P<0.001)。结论半枝莲种素通过HOXA11-AS抑制Wnt/β-catenin信号通路调控肺鳞癌的发生和转移。Objective To investigate the molecular mechanisms by which Rivularin regulates the occurrence and metastasis of lung squamous cell carcinoma.Methods The relative expression levels of target genes in different cell lines were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Animal experiments:Animals were randomly divided into two groups,with the Rivularin animal group received 50 mg·kg^(-1)Rivularin solution daily by gavage;and the model group received an equal volume of 0.9%NaCl daily.Tumor volume was measured.Cell experiments:Cells were divided into control group(no treatment),scutellarin group(3.0 g·L^(-1)scutellarin),scutellarin+oe-HOXA11-AS group(3.0 g·L^(-1)scutellarin extract treatment and transfection of HOXA11-AS),scutellarin+oe-HOXA11-AS+XAV939 group(3.0 g·L^(-1)scutellarin extract treatment,transfection of HOXA11-AS and addition of 10μmol·L^(-1)XAV939).5-ethynyl-2'-deoxyuridine(Edu)and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)assays were used to detect the proliferation and apoptosis rates of cells,respectively;the Transwell assay was used to detect the migration number of NCI-H520 cells in each group.Results The relative expression levels of HOXA11-AS in each lung cancer cell line were significantly higher than those in normal lung epithelial cells(all P<0.05).At 35 days,the tumor volumes of the model group and Rivularin animal group were(937.83±67.40)and(512.32±45.61)mm^(3),respectively;compared between two groups,the difference was statistically significant(P<0.001).The number of cell migration in the control group,Rivularin group,Rivularin+oe-HOXA11-AS group,and Rivularin+oe-HOXA11-AS+XAV939 group were 127.26±8.92,23.76±3.31,131.28±9.49 and 27.69±3.57;the proliferation rates were(56.27±7.49)%,(28.68±4.33)%,(50.12±7.86)%and(13.62±3.54)%respectively;the apoptosis rates were(10.86±2.97)%,(43.23±6.78)%,(30.92±4.53)%and(41.77±7.02)%.The above indicators of the Rivularin group are compared with the control group;the above indicat
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