黏蛋白1基因调控酪氨酸蛋白激酶/信号转导与转录激活因子3信号通路抑制甲状腺癌细胞增殖及促进细胞凋亡机制  

The mechanism of mucin 1 gene by regulated janus protein tyrosine kinase/signal transducer and activators of transcription 3 signaling pathway to inhibit proliferation and promote apoptosis of thyroid cancer cells

作　　者：李红光[1] 赵利红[2] 张振华[1] 高腾[1] 苏自杰 

机构地区：[1]河南省人民医院甲状腺外科,郑州450003 [2]河南省人民医院消毒供应中心,郑州450003

出　　处：《中华实验外科杂志》2017年第11期1889-1891,共3页Chinese Journal of Experimental Surgery

摘　　要：目的探讨黏蛋白1（MUC1）基因调控酪氨酸蛋白激酶（JAK）/信号转导与转录激活因子3（STAT3）信号通路抑制甲状腺癌细胞增殖及促进细胞凋亡的机制。方法Western blot检测甲状腺癌组织和癌旁组织中MUC1表达，将MUC1小干扰RNA（MUC1-siRNA）和阴性对照（siRNA-NC）转染人甲状腺癌细胞SW579，以空脂质体转染的细胞作为对照组，Western blot检测转染效果；细胞转染后培养48 h，细胞计数试剂盒（CCK-8）检测细胞增殖；流式细胞仪检测细胞凋亡；Western blot检测B细胞淋巴瘤/白血病-2相关X蛋白（bax）、B细胞淋巴瘤/白血病-2（bcl-2）、STAT3、磷酸化STAT3（p-STAT3）蛋白表达；细胞中加入15 μmol/L的JAK/STAT3信号通路的特异性抑制剂AG490，记为抑制剂组，不加抑制剂的设为未处理组，CCK-8及流式细胞仪检测两组细胞的增殖和凋亡，Western blot检测bax、bcl-2、STAT3、p-STAT3蛋白表达。结果MUC1在甲状腺癌组织（0.434±0.034）中的表达水平显著高于癌旁组织（0.153±0.018；t＝12.651，P＝0.000）；MUC1-siRNA组细胞存活率[（55.38±7.12）%]、bcl-2（0.237±0.031）、p-STAT3（0.045±0.013）蛋白表达水平显著低于对照组[（94.32±5.21）%、0.425±0.034、0.122±0.025]，细胞凋亡率[（16.29±1.23）%]及bax（0.248±0.026）蛋白表达水平显著高于对照组[（3.06±0.78）%、0.109±0.019]，差异有统计学意义（t存活率＝7.645，P存活率＝0.002；tbcl-2＝7.077，Pbcl-2＝0.002；tp-STAT3＝4.733，Pp-STAT3＝0.009；t凋亡率＝15.733，P凋亡率＝0.000；tbax＝7.476，Pbax＝0.002）。细胞中加入抑制剂后的增殖与凋亡结果与转染MUC1-siRNA的结果一致。结论沉默MUC1的表达能显著抑制人甲状腺癌细胞SW579增殖，并通过调节bcl-2和bax的蛋白表达诱导细胞凋亡，其机制与JAK/STAT3信号通路有关。Objective To investigate the mechanism of membrane type mucin 1 （ MUC1 ） gene by regulated janus protein tyrosine kinase/signal transducer and activators of transcription 3 （ JAK/STAT3 ） signaling pathway to inhibit proliferation and promote apoptosis of thyroid cancer cells. Methods The ex- pression of MUC1 in thyroid carcinoma and adjacent tissues was detected by Western blotting, MUC1 small interfering RNA （MUC1 -siRNA） and negative control （siRNA- NC ） were transfeeted into human thy- roid cancer cells SW579, empty cells as the control group ; cells were transfected for 48 h, Western blotting was used to detect transfection effect ; cell proliferation was detected by cell counting kit - 8 （ CCK - 8 ） ; cell apoptosis was detected by flow cytometry ; the expression of B cell lymphoma/leukemia - 2 associated X protein （ bax）, B cell lymphoma/leukemia - 2 （ bcl - 2）, STAT3, phosphorylated STAT3 （ p - STAT3 ） protein was detected by Western blotting; 15 v, mol/L AG490 specific inhibitor of JAK/STAT3 signaling pathway to join cells as the inhibitor group, without inhibitors for the untreated group, cell proliferation and apoptosis in two group was detected by CCK - 8 and flow cytometry separately; the expression of bax, bcl - 2, STAT3, p - STAT3 protein was detected by Western blotting. Results The expression of MUC1 in thyroid carcinoma tissues （ 0.434 ± 0.034 ） was significantly higher than that in paracancerous tissues （0.153±0.018, t= 12.651, P=0.000）; the cell survival rate [（55.38 ±7.12）%] and bel-2 （0. 237 s0. 031 ）, p- STAT3 （0. 045 ± 0. 013 ） protein expression in MUC1 -siRNA group was signifi- cantly lower than the control group [ （94. 32±5. 21）%, 0. 425 ±0. 034, 0. 122±0. 025], cell apoptosis rate [ （ 16. 29±1.23） % ] and bax （ 0. 248±0. 026） protein expression was significantly higher than the eontrol group [ （3.06±0. 78）% , 0. 109 ±0. 019; tSurvival rate=7. 645, PSurvival rate=0. 002; tbcl-2=7. 077, Pbcl-2 = 0. 002 ; tpSTAT

关 键 词：黏蛋白1 甲状腺癌 增殖 凋亡 

分 类 号：R736.1[医药卫生—肿瘤]