目的 研究红花黄色素调节Wnt/β-catenin信号通路对非霍奇金淋巴瘤(NHL)增殖、凋亡和细胞周期的影响.方法 体外培养Raji细胞,随机分为对照组(常规培养)、红花黄色素组(30 μg·mL-1红花黄色素)、氯化锂组(20 mmol·L-1 LiCl)、红花黄色素+LiCl组(30 μg·mL-1红花黄色素+20 mmol·L-1 LiCl).检测各组细胞Wnt/β-catenin信号通路蛋白表达、细胞增殖、凋亡、细胞周期分布、凋亡及细胞周期相关蛋白表达.裸鼠右前腋皮下接种Raji细胞构建NHL移植瘤模型,随机分为Nu-对照组、Nu-红花黄色素(7.5 mg·kg-1 红花黄色素 LiCl)组、Nu-LiCl(1 mg·kg-1 红花黄色素 LiCl)组、Nu-红花黄色素(7.5 mg·kg-1红花黄色素LiCl)+LiCl(1 mg·kg-1红花黄色素LiCl)组,以红花黄色素和LiCl分组处理后,检测各组裸鼠肿瘤质量和体积.结果 对照组、红花黄色素组、LiCl组、红花黄色素+LiCl组的Wnt1蛋白水平分别为 0.64±0.11、0.19±0.04、1.07±0.40、0.59±0.07,细胞凋亡率分别为(5.13±0.67)％、(57.68±7.31)％、(0.91±0.29)％、(7.24±1.40)％,B-淋巴细胞瘤(Bcl-2)蛋白相对表达水平分别为0.53±0.09、0.09±0.02、0.99±0.14、0.49±0.07,P21蛋白相对表 达水平 分别为0.56±0.12、1.08±0.20、0.13±0.04、0.59±0.11.上述指标:红花黄色素组、LiCl组与对照组相比,红花黄色素+LiCl组与红花黄色素组相比,在统计学上差异均有统计学意义(均P＜0.05).Nu-对照组、Nu-红花黄色素组、Nu-LiCl组、Nu-红花黄色素+LiCl 组的肿瘤体积分别为(915.34±61.43)、(578.46±42.54)、(1 310.84±93.16)和(878.75±56.20)mm3,肿瘤质量分别为(0.86±0.13)、(0.45±0.09)、(1.31±0.15)和(0.75±0.17)g.上述指标:Nu-红花黄色素组、Nu-LiCl组与Nu-对照组相比,Nu-红花黄色素+LiCl组与Nu-红花黄色素组相比,在统计学上差异均有统计学意义(均P＜0.05).结论 红花黄色素可下调Wnt/β-catenin通路蛋白表达,从而诱导NHL细胞周期停滞,抑制其增殖及在裸鼠体内肿瘤生长,并促使其凋亡.
Objective To study the influences of safflower yellow on the proliferation,apoptosis and cell cycle of non-Hodgkin's lymphoma(NHL)by regulating Wnt/β-catenin signaling pathway.Methods Raji cells were cultured in vitro and randomly divided into control group(conventional culture),safflower yellow group(30 μg·mL-1 safflower yellow),lithium chloride group(20 mmol·L-1 LiCl)and safflower yellow+LiCl group(30 μg·mL-1 safflower yellow+20 mmol·L-1 LicL).Cell proliferation,apoptosis,cell cycle distribution,apoptosis and cell cycle related protein expression were detected in each group.Nude mice were subcutaneously inoculated with Raji cells in the right anterior armpit to construct the NHL transplanted tumor model,and they were randomly grouped into Nu-control group,Nu-safflower yellow(7.5 mg·kg-1 safflower yellow)group,Nu-LiCl(1 mg·kg-1 safflower yellow)group,Nu-safflower yellow(7.5 mg·kg-1 safflower yellow)+LiCl(1 mg·kg-1 safflower yellow)group.After grouping and treating with safflower yellow and LiCl,the tumor weight and volume of nude mice in each group were measured.Results The Wnt1 protein levels of control group,safflower yellow group,LiCl group and safflower yellow+LiCl group were 0.64±0.11,0.19±0.04,1.07±0.40 and 0.59±0.07,respectively;the apoptosis rates were(5.13±0.67)％,(57.68±7.31)％,(0.91±0.29)％,(7.24±1.40)％,respectively;the protein levels of B-cell lymphoma-2(Bcl-2)were 0.53±0.09,0.09±0.02,0.99±0.14,0.49±0.07;the protein levels of P21 were 0.56±0.12,1.08±0.20,0.13±0.04,0.59±0.11,respectively.Compared with the control group,there were statistically significant differences of the above indexes between the safflower yellow group and LiCl group,the safflower yellow+LiCl group and the safflower yellow pigment group(all P＜0.05).The tumor volume of Nu-control group,Nu-safflower yellow group,Nu-LiCl group and Nu-safflower yellow+LiCl group was(915.34±61.43),(578.46±42.54),(1 310.84±93.16),(878.75±56.20)mm3,respectively;the tumor weight was(0.86±0.13),(0.45±0.09),(1.31±0.15),(0.75±0.17)g,respectively.Compared with the Nu-control group,there were statistically significant differences of the obove indexes between the Nu-safflower yellow group and Nu-LiCl group,the Nu-safflower yellow+LiCl group and the Nu-safflower yellow pigment group(all P＜0.05).Conclusion Safflower yellow can down regulate the expression of Wnt/β-catenin pathway protein,thereby inducing the cell cycle arrest of NHL cells,inhibiting their proliferation and tumor growth in nude mice,and promoting their apoptosis.
易琰斐;许美瑾;王琪
赣州市肿瘤医院中西医结合科,江西赣州 341000赣州市赣县区人民医院肿瘤科,江西赣州 341000赣州市肿瘤医院肿瘤科,江西赣州 341000
中医学
红花黄色素;非霍奇金淋巴瘤;增殖;凋亡;细胞周期
safflower yellow;non-hodgkin's lymphoma;proliferation;apoptosis;cell cycle
《中国临床药理学杂志》 2024 (006)
839-843 / 5
10.13699/j.cnki.1001-6821.2024.06.012
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