大蒜素促进膀胱肿瘤细胞T24凋亡的JAK/STAT3通路机制研究  

The Involvement of JAK/STAT3 Signaling Pathway in the Apoptosis of T24 Cell Line Induced by Allicin

作　　者：王相平 纪煜航 郑超 李娜 李镇 WANG Xiang-ping;JI Yu-hang;ZHENG Chao;LI Na;LI Zhen(Department of Urology,Dalian Fifth People's Hospital,Dalian,Liaoning,116027,China)

机构地区：[1]大连市第五人民医院泌尿外科,辽宁大连116027

出　　处：《中国血液流变学杂志》2021年第4期452-457,472,共7页Chinese Journal of Hemorheology

基　　金：大连市医学科学研究计划项目(1811059)。

摘　　要：目的探讨膀胱肿瘤细胞T24凋亡的JAK/STAT3通路参与作用及大蒜素促进细胞凋亡的相关机制,为临床治疗提供参考。方法T24肿瘤细胞随机分为5组:对照组、ADZ1480组、大蒜素1组(1μmol/L)、大蒜素2组(10μmol/L)和大蒜素3组(100μmol/L)。肿瘤细胞经相应药物处理后,MTT法检测肿瘤细胞的增殖抑制率,Western blotting法检测细胞凋亡蛋白Bax/Bcl2、Caspase 3和Caspase 9蛋白及JAK/STAT信号转导通路蛋白JAK1、JAK2、JAK3和STAT1及STAT3表达,并检测细胞内基质金属蛋白酶及其抑制剂的表达情况。结果MTT结果发现ADZ1480及大蒜素均能有效抑制T24肿瘤细胞的增殖,且抑制效果具有时间和剂量依从性(P<0.05,P<0.01);药物处理后细胞凋亡蛋白Bax及Caspase 3和Caspase 9表达升高而Bcl2表达降低(P<0.01),JAK通路蛋白JAK1、JAK2、JAK3和STAT1及STAT3表达升高(P<0.01),基质金属蛋白酶MMP2、MMP9和MMP12及其抑制剂TIMP1和TIMP2表达明显升高(P<0.01),也具有剂量依从性效果。结论大蒜素能够有效抑制膀胱肿瘤细胞T24增殖、促进其凋亡,其可能是通过抑制肿瘤细胞中过度激活的JAK/STAT通路实现的。Objective To explore the involvement of JAK/STAT3 pathway in bladder tumor cell T24 apoptosis and the related mechanism of allicin in promoting cell apoptosis,so as to provide reference for clinical treatment.Methods T24 cell line were divided into 5 groups randomly,control group,ADZ1480 group,allicin group 1(1μmol/L),allicin group 2(10μmol/L)and allicin group 3(100μmol/L).The inhibition rate of drugs was detected by MTT methods.After tumor cells were treated with corresponding drugs,the proliferation inhibition rate of tumor cells was detected by MTT method,the expression of apoptosis proteins Bax/Bcl2,Caspase 3 and Caspase 9 and JAK/STAT signal transduction pathway proteins JAK1,JAK2,JAK3,STAT1 and STAT3 were detected by Western blotting method,and the expression of intracellular matrix metalloproteinases and their inhibitors was detected.Results MTT results showed that both ADZ1480 and allicin could effectively inhibited the proliferation of T24 tumor cells,and the inhibitory effect was time-and dose-dependent(P<0.05,P<0.01).After drug treatment,the expression of apoptosis proteins Bax,caspase 3 and caspase 9 increased,while the expression of Bcl2 decreased(P<0.01),the expression of JAK pathway proteins JAK1,JAK2,JAK3,STAT1 and STAT3 increased(P<0.01),and the expression of matrix metalloproteinases MMP2,MMP9 and MMP12 and their inhibitors TIMP1 and TIMP2 increased significantly(P<0.01),which also had a dose-dependent effect.Conclusion Allicin can effectively inhibit the proliferation of bladder tumor cell T24 and promote its apoptosis,which may be achieved by inhibiting the over activated JAK/STAT pathway in tumor cells.

关 键 词：大蒜素 膀胱癌 细胞凋亡 JAK/STAT信号转导通路 抑制率 剂量依从性 

分 类 号：R73-3[医药卫生—肿瘤] R737.14[医药卫生—临床医学]