褪黑素与阿霉素协同诱导人肝癌细胞系凋亡。
Melatonin and doxorubicin synergistically induce cell apoptosis in human hepatoma cell lines.
机构信息
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China.
出版信息
World J Gastroenterol. 2010 Mar 28;16(12):1473-81. doi: 10.3748/wjg.v16.i12.1473.
AIM
To investigate whether melatonin has synergistic effects with doxorubicin in the growth-inhibition and apoptosis-induction of human hepatoma cell lines HepG2 and Bel-7402.
METHODS
The synergism of melatonin and doxorubicin inhibited the cell growth and induced cell apoptosis in human hepatoma cell lines HepG2 and Bel-7402. Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using TUNEL method and flow cytometry. Apoptosis-related protein Bax, Bcl-2 and caspase-3 expressions were measured by immunohistochemical staining.
RESULTS
Treatment with melatonin (10(-8)-10(-5) mol/L) alone had a dose-related inhibitory effect on cell proliferation but no cytotoxic effect on hepatoma cell lines HepG2 and Bel-7402. Interestingly, when combined with doxorubicin, melatonin significantly increased the effects of cell growth inhibition and cell apoptosis. Furthermore, TUNEL staining and flow cytometry revealed that cooperative apoptosis induction was associated with decreased expression of Bcl-2 as well as increased expression of Bax and Caspase3.
CONCLUSION
The synergism of melatonin and doxorubicin inhibits hepatoma cell growth and induces cell apoptosis.
目的
探讨褪黑素（melatonin）与阿霉素（doxorubicin）联合应用对人肝癌细胞株 HepG2 和 Bel-7402 生长抑制和凋亡诱导的协同作用。
方法
采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法检测褪黑素（10(-8)-10(-5) mol/L）单用及与阿霉素联合应用对 HepG2 和 Bel-7402 细胞生长的抑制作用，采用原位末端标记法（TUNEL）和流式细胞术检测细胞凋亡，免疫组化法检测凋亡相关蛋白 Bax、Bcl-2 和 caspase-3 的表达。
结果
褪黑素（10(-8)-10(-5) mol/L）单用对 HepG2 和 Bel-7402 细胞增殖有剂量依赖性抑制作用，但无细胞毒性。有趣的是，褪黑素与阿霉素联合应用可显著增强对细胞生长抑制和凋亡的作用。TUNEL 染色和流式细胞术结果显示，协同诱导的细胞凋亡与 Bcl-2 表达降低以及 Bax 和 Caspase3 表达增加有关。
结论
褪黑素与阿霉素具有协同抑制肝癌细胞生长和诱导细胞凋亡的作用。
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