氮烯咪胺对垂体瘤大鼠及垂体瘤GH3细胞的影响  

Effect of dacarbazine in rats with pituitary tumor and pituitary tumor GH3 cells

作　　者：李邦安 姜之全[2] LI Bang-an;JIANG Zhi-quan(Department of Neurosurgery,Lu’an Hospital Affiliated to Anhui Medical University,Lu’an Peoples Hospital,Anhui Province,Lu’an 237005,Anhui Province,China;Department of Neurosurgery,First Affiliated Bengbu Hospital of Bengbu Medical College,the Cancer Hospital to Bengbu Medical College,Bengbu 233030,Anhui Province,China)

机构地区：[1]安徽医科大学附属六安医院、六安市人民医院神经外科,安徽六安237005 [2]蚌埠医学院第一附属医院、蚌埠医学院附属肿瘤医院神经外科,安徽蚌埠233030

出　　处：《中国临床药理学杂志》2021年第16期2198-2200,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探究氮烯咪胺对垂体瘤大鼠细胞丝裂原活化蛋白激酶(MEK)/细胞外调节蛋白激酶(ERK)信号通路的影响及其作用机制。方法建立垂体瘤荷瘤模型,将荷瘤裸鼠随机分组为对照组和低、中、高剂量实验组。对照组腹腔注射生理盐水,低、中、高剂量实验组分别用1,3,6 mg·kg^(-1)氮烯咪胺处理裸鼠,每2天1次连续2周,测量肿瘤体积。用0,5,10,20,40μmol·L^(-1)氮烯咪胺培养大鼠垂体瘤GH3细胞,用流式细胞仪检测细胞凋亡情况,用蛋白质印迹(Western blot)法检测MEK、ERK、B淋巴细胞瘤(Bcl-2)蛋白质表达情况。结果对照组和低、中、高剂量实验组裸鼠的肿瘤体积分别为(875.15±63.87),(541.13±78.84),(532.46±30.89),(379.09±44.84)mm^(3),差异有统计学意义(P<0.05)。0,5,10,20,40μmol·L^(-1)氮烯咪胺组GH3细胞的凋亡率分别为(3.15±0.84)%,(28.38±7.86)%,(31.63±3.39)%,(53.55±3.69)%,(59.39±3.00)%,Bcl-2蛋白表达量分别为1.31±0.07,1.28±0.02,1.15±0.01,0.81±0.02,0.55±0.02,p-MEK蛋白表达量分别为1.48±0.02,1.41±0.02,0.93±0.01,0.81±0.04,0.51±0.01,p-ERK蛋白表达量分别为1.40±0.02,1.28±0.05,0.84±0.01,0.67±0.03,0.43±0.04,差异均有统计学意义(均P<0.05)。结论氮烯咪胺对大鼠垂体瘤具有显著的抑制作用,其机制可能是诱导大鼠垂体瘤细胞的凋亡,抑制MEK/ERK信号通路的磷酸化,发挥剂量依赖性的抗肿瘤作用。Objective To investigate the effect of dacarbazine on mitogen-activated protein kinase(MEK)/extracellular regulated protein kinases(ERK) signaling pathway in pituitary tumor rats and its mechanism. Methods Pituitary tumor model was established and tumor bearing nude mice were randomly divided into control group and low, medium, high dose experimental groups. Control group was intraperitoneally injected with normal saline, and nude mice in low, medium, high dose experimental group were treated with 1, 3 and 6 mg·kg-1 dacarbazine, respectively, once every 2 days for 2 weeks, tumor volume was measured. GH3 cells were cultured with 0, 5, 10, 20, 40 μmol·L-1 dacarbazine, and the apoptosis of GH3 cells was detected by flow cytometry, Western blot were used to detect the expression of MEK, ERK and B cell lymphoma-2(Bcl-2). Results The tumor volume of nude mice in control group and low, medium, high dose experimental groups were( 875. 15 ± 63. 87),( 541. 13 ± 78. 84),( 532. 46 ± 30. 89) and( 379. 09 ± 44. 84)mm3,with significant difference( P < 0. 05). After treatment,the apoptosis rates of 0,5,10,20 and 40 μmol·L-1 dacarbazine groups GH3 cells were( 3. 15 ± 0. 84) %,( 28. 38 ± 7. 86) %,( 31. 63 ± 3. 39) %,( 53. 55 ± 3. 69) %,( 59. 39 ± 3. 00) %,the expression levels of Bcl-2 protein were 1. 31 ± 0. 07,1. 28 ± 0. 02,1. 15 ± 0. 01,0. 81 ± 0. 02,0. 55 ± 0. 02,the expression levels of p-MEK protein were 1. 48 ± 0. 02,1. 41 ± 0. 02,0. 93 ± 0. 01,0. 81 ± 0. 04,0. 51 ± 0. 01,the expression levels of p-ERK protein were 1. 40 ± 0. 02,1. 28 ± 0. 05,0. 84 ± 0. 01,0. 67 ± 0. 03,0. 43 ± 0. 04,all with significant difference( all P < 0. 05). Conclusion Dacarbazine has significant inhibitory effect on rat pituitary adenoma. The mechanism may induce apoptosis of rat pituitary adenoma cells,inhibit the phosphorylation of MEK/ERK signaling pathway,and play a dose-dependent anti-tumor effect.

关 键 词：氮烯咪胺 垂体瘤 细胞丝裂原活化蛋白激酶激酶/细胞外调节蛋白激酶信号通路 

分 类 号：R979.1[医药卫生—药品]