硒-甲基硒代半胱氨酸对肝癌HepG2 细胞的抑制作用

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (3): 286-291.

硒-甲基硒代半胱氨酸对肝癌HepG₂ 细胞的抑制作用

史传兵, 卢航青, 郑杰

东南大学基础医学院病理与病理生理学系,分子病理研究所,南京 210009,江苏

收稿日期:2005-11-03 修回日期:2005-12-15 出版日期:2006-03-26 发布日期:2020-12-04
通讯作者: 郑杰,男,博士,教授,硕士研究生导师,研究方向:分子肿瘤学。Tel:025-83272358 E-mail:jiezheng54@126.com
作者简介:史传兵,男,硕士研究生,研究方向:分子肿瘤学。E-mail:chuanbingshi78@126.com
基金资助:
江苏省自然科学基金项目(NoBK2005070)

Inhibition on liver carcinoma cells HepG₂ by Se-methylselenocysteine

SHI Chuan-bing, LU Hang-qing, ZHENG Jie

Institute of Molecular Pathology,Department of Pathology and Pathophysiology,School of Basic Medical Science,Southeast University,Nanjing 210009,Jiangsu,China

Received:2005-11-03 Revised:2005-12-15 Online:2006-03-26 Published:2020-12-04

摘要/Abstract

摘要： 目的研究硒-甲基硒代半胱氨酸(Se-methylselenocysteine,MSC)对肝癌HepG₂细胞增殖及凋亡的影响,探讨其分子机制。方法: 用不同浓度的MSC处理培养的HepG₂细胞,镜下观察细胞的形态学变化,MTT法和流式细胞仪分别检测其对细胞生长和细胞周期的影响,软琼脂生长试验观察瘤细胞恶性表型的变化,并检测细胞周期蛋白D1(CyclinD1)mRNA的表达和半胱氨酸蛋白酶-3(Caspase-3)的活性。结果: 25μmol·L^-1的MSC处理HepG₂细胞24h后,细胞生长受到明显抑制,出现S期阻滞和细胞凋亡,呈现浓度和时间依赖关系。软琼脂生长试验显示MSC抑制HepG₂细胞在软琼脂上的生长能力。RT-PCR和Caspase-3的活性检测显示,25μmol·L^-1MSC处理HepG₂细胞24、48h后,Cyclin D1 mRNA表达下降了38%和47%,而Caspase-3活性分别升高(39.61±6.65)%和(118.73±6.48)%;50μmol·L^-1MSC处理HepG₂细胞24、48h后,Cyclin D1 mRNA表达下降了53%和82%,而Caspase-3活性分别升高(80.66±9.31)%和(152.67±7.95)%。结论: MSC抑制HepG₂细胞增殖,诱导其凋亡,瘤细胞的恶性程度减弱,这种表型变化与CyclinD1的表达减弱和Caspase-3的活性增强有关。

关键词: 硒-甲基硒代半胱氨酸, HepGHepG₂细胞, 细胞凋亡, 细胞周期, 恶性表型

Abstract: AIM: To study the effects of Se-methylselenocysteine(MSC) on the growth and apoptosis of human liver carcinoma cell line,HepG₂ cells and the molecular mechanism of effects.METHODS: After HepG₂ cells treated with various concentrations of MSC,survival and apoptosis were determined by MTT assay and light microscope,apoptosis and cell cycle were determined by flow cytometry.Malignant phenotype was determined by soft agarose growth assay.Cyclin D1 mRNA expression was determined by RT-PCR and Caspase-3 activity was measured by Caspase-3 activity assay kit.RESULTS: After being treated with 25 μmol·L^-1 MSC for 24 h,the survival of HepG₂ cells was decreased,a marked apoptosis and S phase arrest characteristic was observed in timeand dose- dependent manner.Soft agatose growth assay showed MSC inhibited HepG₂ cells growth in soft agarose.RT-PCR and Caspase-3 assay showed that HepG₂ cells treated with 25 μmol·L^-1 MSC for 24 and 48 hours,the expression of Cyclin D1 mRNA was down-regulated by 38% and 47%,while Caspase-3 activity was up-regulat-ed by (39.61±6.65)%and (118.73±6.48)%.Hep-G2 cells treated with 50 μmol·L^-1 MSC for 24 and 48 h,the expression of Cyclin D1 mRNA was down-regulated by 53% and 82%,whereas Caspase-3 activity was up-regulated by (80.66±9.31)% and (152.67±7.95)%.CONCLUSION: MSC can inhibit the growth of HepG₂ cells,and induce apoptosis and S phase arrest of HepG₂ cells.The phenotype alterations of HepG₂ cells might relate with inhibition of Cyclin D1 expression and Caspase-3activity by MSC in the cells.

Key words: Se-methylselenocysteine, HepG₂ cell, apoptosis, cell cycle, malignant phenotype

中图分类号:

R979.1

史传兵, 卢航青, 郑杰. 硒-甲基硒代半胱氨酸对肝癌HepG₂ 细胞的抑制作用[J]. 中国临床药理学与治疗学, 2006, 11(3): 286-291.

参考文献

1 Yeo JK,Cha SD,Cho CH,Kim SP,Cho JW,Baek WK,et al.Se-methylselenocysteine induces apoptosis through caspase activation and Bax cleavage mediated by calpain in SKOV-3 ovarian cancer cells[J].Cancer Lett,2002;182:83-92
2 Medina D,Thompson H,Ganther H,Ip C.Se-methylselenocysteine:a new compound for chemoprevention of breast cancer[J].Nutr Cancer,2001;40:12-7
3 Jiang C,Wang Z,Ganther H,Lu J.Caspases as key executors of methyl selenium-induced apoptosis (anoikis) of DU-145 prostate cancer cells[J].Cancer Res,2001;61:3062-70
4 Jung U,heng X,Yoon SO,Chung AS.Se-methylselenocysteine induces apoptosis mediated by reactive oxygen species in HL-60 cells[J].Free Radic BiolMed,2001;31:479-89
5 Yata K,Sadahira Y,Otsuki T,Sakaguchi H,Isozaki Y,Uno M,et al.Cell cy cle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cy clin D1[J].Br J Haematol,2001;114:591-9
6 El-Bayoumy K,Sinha R.Mechanisms of mammary cancer chemoprevention by organoselenium compounds[J].Mutat Res,2004;551:181-97
7 Muramatsu T,Shima K,Ohta K,Kizaki H,Ro Y,Kohno Y,et al.Inhibition of osteopontin expression and function in oral cancer cell lines by antisense oligonucleotides[J].Cancer Lett,2005;217:87-95
8 Unni E,Kittrell FS,Singh U,Sinha R.Osteopontin is a potential target gene in mouse mammary cancer chemoprevention by Semethylselenocysteine[J].Breast Cancer Res,2004;6:R586-92
9 候志波,郑杰.骨桥蛋白下调对前列腺癌PC3 细胞生物学行为的影响[J].肿瘤,2005;25:542-6
10 Unni E,Koul D,Yung WK,Sinha R.Se-methylselenocysteine inhibits phosphatidylinositol 3-kinase activity of mouse mammary epithelial tumor cells in vitro[J].Breast Cancer Res,2005;7:R699-707
11 Zhang GX,Zhao ZQ,Wang HD,Hao B.Enhancement of osteopontin expression in HepG2 cells by epidermal growth factor via phosphatidylinositol 3-kinase signaling pathway[J].World J Gastroenterol,2004;10:205-8
12 Serrano M,Hannon GJ,Beach D.A new regulatory motif in cellcycle control causing specific inhibition of cyclin D CDK4[J].Nature,1993;366:704-7
13 Sinha R,Kiley SC,Lu JX,Thompson HJ,Moraes R,Jaken S,et al.Effects of methylselenocysteine on PKC activity,cdk2 phosphorylation and gadd gene expression in synchronized mouse mammary epithelial tumor cells[J].Cancer Lett,1999;146:135-45
14 El-Bayoumy K,Narayanan BA,Desai DH,Narayanan NK,Pittman B,Amin SG,et al.Elucidation of molecular targets of mammary cancer chemoprevention in the rat by organoselenium compounds using cDNA microarray[J].Carcinogenesis,2003;24:1505-14
15 Green DR,Reed JC.Mitochondria and apoptosis[J].Science,1998;281:1309-12

[1]	杨晓佳, 江萌, 吴敏, 张伊黎, 吕兰, 吴嫄芬, 王鑫昱, 刘立权. 藏红花素介导DKK3调控GSK-3β/β-catenin通路对阿尔兹海默症大鼠的认知改善作用[J]. 中国临床药理学与治疗学, 2023, 28(5): 489-497.
[2]	王剑, 孙永东, 周兴玮, 刘雷, 陈龙, 童兴科, 朱佳丽. 黄芩素经由miR-125b-5p/IRF4轴进而促进喉癌细胞死亡并抑制其侵袭的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1209-1218.
[3]	华海燕, 严杰, 秦宇芬. 五味子乙素通过抑制心肌细胞凋亡减轻大鼠心肌缺血再灌注损伤的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 848-856.
[4]	李雪恒, 李龙. 褪黑素与特发性肺纤维化关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 715-720.
[5]	李莹, 姚伟, 王萌, 余志宏, 龚园其, 蓝海兵, 齐协飞. 鸢尾素通过NF-κB和JNK信号通路减轻屋尘螨诱导的气道上皮细胞炎症及凋亡的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(10): 1106-1112.
[6]	叶凯丽, 郑雯, 叶啟发, 杨岚. CDK1参与肝细胞癌的发展机制及其抑制剂应用价值[J]. 中国临床药理学与治疗学, 2021, 26(9): 1086-1094.
[7]	刘云帆, 杜月梅, 刘晓艺, 高丽萍. 枸杞多糖对顺铂诱导小鼠睾丸支持细胞凋亡的影响[J]. 中国临床药理学与治疗学, 2021, 26(6): 624-630.
[8]	张伟萍, 江建军, 陈晓锋, 许莎莎. 栀子苷通过抑制VPO1/ERK1/2信号通路减轻糖尿病心肌病大鼠的心肌细胞凋亡[J]. 中国临床药理学与治疗学, 2021, 26(2): 129-136.
[9]	沈芸, 张占丰, 王红灵, 赵冀安. 丹酚酸对大鼠骨骼肌缺血再灌注损伤的保护[J]. 中国临床药理学与治疗学, 2020, 25(10): 1111-1118.
[10]	吴丽梅，程丽艳，郑晓亮，王孝举. 靶向抑制CDK4/6的肿瘤治疗基础研究与临床应用进展[J]. 中国临床药理学与治疗学, 2019, 24(9): 1065-1069.
[11]	滕晓晶，董学妍，王智毅，余道军，王贤军. 扶正康复合剂联合顺铂抑制胃癌SGC7901细胞荷瘤裸鼠肿瘤增殖作用的实验研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 744-749.
[12]	孔令宇，席錾，杨亚勤，马文婷，吴畏，郝同琴. 地塞米松对小鼠急性胰腺炎胰腺组织中Notch信号及凋亡相关基因表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(2): 134-139.
[13]	齐冰丽，黄平，颜瑞雪，李倩. 柚皮素通过PI3K/AKT/NF-κB通路抑制卵巢癌细胞增殖和侵袭、诱导凋亡作用的研究[J]. 中国临床药理学与治疗学, 2019, 24(11): 1234-1241.
[14]	曹迎亚，陈群，王箴，吴敬医，姜小敢，金孝岠，鲁卫华. 巨噬细胞在脂多糖诱导肠上皮细胞凋亡中的作用[J]. 中国临床药理学与治疗学, 2019, 24(10): 1142-1146.
[15]	秦博宇，王刚，齐晓光，王雅捷，孙琼，孙胜杰 . 顺铂与唑来膦酸序贯应用抑制肺癌细胞增殖的研究[J]. 中国临床药理学与治疗学, 2018, 23(9): 1027-1030.

硒-甲基硒代半胱氨酸对肝癌HepG₂ 细胞的抑制作用

Inhibition on liver carcinoma cells HepG₂ by Se-methylselenocysteine

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价