网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
HMGB1对胆囊癌细胞增殖、凋亡的影响及其机制研究
作者:张斌  陶健  赵慈宝  闵北卿  王坦 
单位:上海市徐汇区大华医院 外科, 上海 200237
关键词:胆囊癌 凋亡 增殖 高迁移率蛋白1 
分类号:R735.8
出版年·卷·期(页码):2017·36·第十期(1422-1426)
摘要:

目的:探讨高迁移率蛋白1(HMGB1)对胆囊癌细胞增殖、凋亡的影响及其机制。方法:胆囊癌细胞GBC-SD转染HMGB1小干扰RNA(HMGB1 siRNA)、siRNA阴性对照,分别记为干扰组和siRNA-NC组,以不转染的细胞为对照组。RT-PCR和蛋白质印迹法分别检测转染效果,噻唑蓝(MTT)法检测细胞增殖,流式细胞仪检测细胞凋亡,蛋白质印迹法检测β-连环蛋白、c-myc和活化的含半胱氨酸的天冬氨酸蛋白水解酶3的表达。结果:对照组和siRNA-NC组细胞中HMGB1 mRNA和蛋白表达水平[光密度值(OD值)]、细胞凋亡率、β-连环蛋白、c-myc和活化的含半胱氨酸的天冬氨酸蛋白水解酶3表达水平没有明显变化。干扰组HMGB1 mRNA和蛋白表达水平及β-连环蛋白、c-myc表达水平明显低于对照组,而细胞凋亡率明显高于对照组,差异具有统计学意义(P<0.05)。结论:干扰HMGB1可能通过调控Wnt信号通路抑制胆囊癌细胞增殖,促进胆囊癌细胞凋亡。

Objective: To investigate the effect of HMGB1 on proliferation and apoptosis of gallbladder cancer cells and its mechanism. Methods: The gallbladder cancer cell GBC-SD transfected with HMGB1 siRNA and siRNA control was used as interference group and siRNA -NC group, and the non transfected cells were served as control group. The transfection efficiency was monitored by RT-PCR and Western blot, the cell proliferation and apoptosis were respectively detected by MTT and flow cytometry, and the expressions of β-catenin, c-myc and Cleaved Caspase-3 were detected by Western blot. Results: No significant changes of HMGB1 mRNA and protein, β-catenin, c-myc and Cleaved Caspase-3 levels(OD value), apoptosis rate were found in siRNA-NC group compared with those in the control group.HMGB1 mRNA and protein, β-catenin and c-myc in the interference group were obviously decreased compared with those in the control group, while the apoptosis rate and Cleaved Caspase-3 were obviously increased, the difference being statistically significant(P<0.05). Conclusion: Interference with HMGB1 may inhibit the proliferation of gallbladder cancer cells by regulating the Wnt signaling pathway.

参考文献:

[1] BAIG M,GUARINO M,PETRELLI N.Report on demographics of gall bladder cancer in Delaware and retrospective review of treatment strategies for gallbladder cancer in a large community cancer center[J].Surg Oncol,2016,25(2):86-91.
[2] CREASY J M,GOLDMAN D A,DUDEJA V,et al.Systemic chemotherapy combined with resection for locally advanced gallbladder carcinoma:surgical and survival outcomes[J].J Am Coll Surg,2017,224(5):906-916.
[3] ETHUN C G,POSRLEWAIT L M,LE N,et al.A novel pathology-based preoperative risk score to predict locoregional residual and distant disease and survival for incidental gallbladder cancer:a 10-institution study from the US Extrahepatic Biliary Malignancy Consortium[J].Ann Surg Oncol,2017,24(5):1343-1350.
[4] YAMAZAKI T,HANNANI D,POIRIER-COLAME V,et al.Defective immunogenic cell death of HMGB1-deficient tumors:compensatory therapy with TLR4 agonists[J].Cell Death Differ,2014,21(1):69-78.
[5] LADOIRE S,PENAULT-LIORCA F,SENOXILLA L,et al.Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer[J].Autophagy,2015,11(10):1878-1890.
[6] LADOIRE S,ENOT D,SENOVILLA L,et al.The presence of LC3B puncta and HMGB1 expression in malignant cells correlate with the immune infiltrate in breast cancer[J].Autophagy,2016,12(5):864-875.
[7] TAKEBE N,MIELE L,HARRIS P J,et al.Targeting Notch,Hedgehog,and Wnt pathways in cancer stem cells:clinical update[J].Nat Rev Clin Oncol,2015,12(8):445-464.
[8] CHANG B,WANG D,XING J,et al.miR-200c inhibits metastasis of breast cancer cells by targeting HMGB1[J].J Huazhong Univ Sci Technolog Med Sci,2014,34(2):201-206.
[9] LIU W,ZHANG Z,ZHANG Y,et al.HMGB1-mediated autophagy modulates sensitivity of colorectal cancer cells to oxaliplatin via MEK/ERK signaling pathway[J].Cancer Biol Ther,2015,16(4):511-517.
[10] UEDA M,TAKAHASHI Y,SHINDEN Y,et al.Prognostic significance of high mobility group box 1(HMGB1) expression in patients with colorectal cancer[J].Anticancer Res,2014,34(10):5357-5362.
[11] ZHANG Q Y,WU L Q,ZHANG T,et al.Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2[J].Oncol Rep,2015,33(4):1630-1638.
[12] LI W,WU K,ZHAO E,et al.HMGB1 recruits myeloid de-rived suppressor cells to promote peritoneal dissemination of colon cancer after resection[J].Biochem Biophys Res Commun,2013,436(2):156-161.
[13] ROY A,GANESH G,SIPPOLA H,et al.Mast cell chymase degrades the alarmins heat shock protein 70,biglycan,HMGB1,and interleukin-33(IL-33) and limits danger-induced inflammation[J].J Biol Chem,2014,289(1):237-250.
[14] GUAN X,WANG P,CHI J,et al.Relationships of BRAF mutation and HMGB1 to papillary thyroid carcinoma[J].Biochem Biophys Res Commun,2017,486(4):898-903.
[15] ZHANG W,TIAN J,HAO Q.HMGB1 combining with tumor-associated macrophages enhanced lymphangiogenesis in human epithelial ovarian cancer[J].Tumour Biol,2014,35(3):2175-2186.
[16] 白明辉,孙君军,董玉宁,等.HMGB1在胆囊癌组织中的表达及意义[J].中国现代普通外科进展,2014,17(7):563-564.
[17] ABE A,KUWATA T,YAMAUCHI C,et al.High Mobility Group Box1(HMGB1) released from cancer cells induces the expression of pro-inflammatory cytokines in peritoneal fibroblasts[J].Pathol Int,2014,64(6):267-275.
[18] 韩秋荣,张璐,盛修贵.HMGB1-siRNA对卵巢癌细胞OV5生物学活性影响研究[J].中华肿瘤防治杂志,2015,22(14):1109-1114.
[19] 张丹,吕亮,申兴斌,等.大肠癌中Survivin,NF-κB,I-κB及Caspase-3的表达及意义[J].中国老年学杂志,2017,37(3):549-552.
[20] 张倩璐,邓珊,江青山,等.SAA蛋白与BCL-2、Caspase-3及NF-κB关系的研究[J].东南大学学报:医学版,2015,34(2):191-195.
[21] WANG G,LI Z,ZHAO Q,et al.LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway[J].Oncol Rep,2014,31(4):1839-1845.
[22] 董星,董海峰,梁马可,等.β-连环蛋白和膜突蛋白在胆囊癌中的表达及其意义[J].中国实用医刊,2013,40(12):1-4.
[23] PRASAD C P,RATH G,MATHUR S,et al.Potent growth suppressive activity of curcumin in human breast cancer cells:Modulation of Wnt/β-catenin signaling[J].Chem Biol Interact,2009,181(2):263-271.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 746924 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541