双氢青蒿素对神经母细胞瘤细胞生长的抑制作用及其机制

doi:10.13481/j.1671-587x.20160215

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (02): 266-270.doi: 10.13481/j.1671-587x.20160215

双氢青蒿素对神经母细胞瘤细胞生长的抑制作用及其机制

齐玲¹, 杨阳¹, 刘玉翠¹, 朱天信¹, 金嵩¹, 臧琳¹, 张玉影¹, 吕鹏¹, 徐冶²

1. 吉林医药学院病理教研室, 吉林吉林 132013;
2. 吉林医药学院科研实验室, 吉林吉林 132013

收稿日期:2015-09-15 发布日期:2016-03-31
通讯作者: 徐冶,教授,硕士研究生导师(Tel:0432-64560371,E-mail:xuye_9707@163.com) E-mail:xuye_9707@163.com
作者简介:齐玲(1974-),女,吉林省吉林市人,副教授,医学博士,主要从事脑肿瘤方面的研究。
基金资助:
国家自然科学基金资助课题(81201671);吉林省科技厅科研基金资助课题(20140414049GH);吉林省卫生厅科研基金资助课题(2014Z104)

Inhibitory effect of dihydroartemisinin on growth of neuroblastoma cells and its mechanism

QI Ling¹, YANG Yang¹, LIU Yucui¹, ZHU Tianxin¹, JIN Song¹, ZANG Lin¹, ZHANG Yuying¹, LYU Peng¹, XU Ye²

1. Department of Pathology, Jilin Medical University, Jilin 132013, China;
2. Medical Research Laboratory, Jilin Medical University, Jilin 132013, China

Received:2015-09-15 Published:2016-03-31

摘要/Abstract

摘要：

目的: 探讨双氢青蒿素(DHA)对神经母细胞瘤细胞生长的抑制作用,阐明DHA抗神经母细胞瘤的作用机制。方法: 实验分为空白对照组和DHA组(DHA终浓度分别为0.05、0.50、5.00和50.00 μmol·L^-1)。采用MTT法检测DHA作用后SH-SY5Y细胞的增殖率,流式细胞术分析DHA作用后SH-SY5Y细胞周期的变化,ELISA和Western blotting法分析DHA作用后SH-SY5Y细胞中cyclin D1和caspase-3蛋白表达水平的变化。结果: 不同浓度DHA作用SH-SY5Y细胞24、48和72h时均可抑制细胞的生长,与空白对照组比较,0.50、5.00和50.00 μmol·L^-1 DHA组SH-SY5Y细胞增殖率明显下降(P<0.05或P<0.01);细胞生长的密度随药物浓度的升高而降低。与空白对照组比较,50.00 μmol·L^-1 DHA组SubG₁期细胞的百分比增加(P<0.05);G₀/G₁期细胞百分比先升高再降低,S期与G₂/M期细胞的百分比减少。与空白对照组比较,50.00 μmol·L^-1 DHA组SH-SY5Y细胞中cyclinD1蛋白表达水平降低(P<0.05);与空白对照组比较,50.00 μmol·L^-1DHA组caspase-3蛋白表达水平升高(P<0.05)。结论: DHA可能通过阻滞肿瘤细胞周期、促进肿瘤细胞凋亡而抑制神经母细胞瘤细胞的生长。

关键词: 双氢青蒿素, 神经母细胞瘤, cyclin D1, caspase-3

Abstract:

Objective: To explore the inhibitory effect of dihydroartemisinin (DHA) on the growth of neuroblastoma cells, and to clarify the anti-tumor mechanism of DHA.Methods: The experiment was divided into blank control group and DHA groups (the final concentrations of DHA were 0.05, 0.50, 5.00 and 50.00 μmol·L^-1).The proliferation rates of neuroblastoma SH-SY5Y cells after treated with DHA were examined by MTT assay; the changes of cell cycle of SH-SY5Y cells after treated with DHA were examined by flow cytometry;the expression levels of cyclin D₁ and caspase-3 proteins were detected by ELISA and Western blotting methods.Results: The proliferation of SH-SY5Y cells 24, 48, and 72 h after treated with different concentrations of DHA were inhibited.Compared with blank control group, the proliferation rates of SH-SY5Y cells in 0.50, 5.00 and 50.00 μmol·L^-1DHA groups were significantly decreased(P<0.05 or P<0.01).The density of cells was decreased with the increasing of DHA concentration.Compared with blank control group, the percentage of SH-SY5Y cells at SubG₁ phase in 50.00 μmol·L^-1 DHA group was increased(P<0.05), and the percentage of cells at G₀/G₁ phase was increased first then was decreased; otherwise, the percentages of cells at S and G₂/M phase were decreased.Compared with blank control group, the expression level of cyclin D1 protein in 50.00 μmol·L^-1 DHA group was decreased(P<0.05), but the expression level of caspase-3 protein in 50.00 μmol·L^-1 DHA group was increased(P<0.05).Conclusion: DHA could inhibit the proliferation through arresting the cell cycle and inducing the apoptosis of neuroblastoma cells.

Key words: dihydroartemisinin, neuroblastoma cells, cyclin D1, caspase-3

中图分类号:

R739.4

齐玲, 杨阳, 刘玉翠, 朱天信, 金嵩, 臧琳, 张玉影, 吕鹏, 徐冶. 双氢青蒿素对神经母细胞瘤细胞生长的抑制作用及其机制[J]. 吉林大学学报(医学版), 2016, 42(02): 266-270.

QI Ling, YANG Yang, LIU Yucui, ZHU Tianxin, JIN Song, ZANG Lin, ZHANG Yuying, LYU Peng, XU Ye. Inhibitory effect of dihydroartemisinin on growth of neuroblastoma cells and its mechanism[J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 266-270.

参考文献

[1] Ryu NG,Moon IJ,Chang YS,et al.Cochlear implantation for profound hearing loss after multimodal treatment for neuroblastoma in Children[J].Clin Exp Otorhinolaryngol,2015,8(4):329-334.

[2] Xu CC,Deng T,Fan ML,et al.Synthesis and in vitroantitumor evaluation of dihydroartemisinin-cinnamic acid ester derivatives[J]. Eur J Med Chem,2015,107(5):192-203.

[3] Hou J,Wang D,Zhang R,et al.Experimental therapy of hepatoma with artemisinin and its derivatives:in vitro and in vivo activity,chemosensitization,and mechanisms of action[J].Clin Cancer Res,2008,14(17):5519-5530.

[4] Kim SJ,Kim MS,Lee JW,et al.Dihydroartemisinin enhances radiosensitivity of human glioma cells in vitro[J].J Cancer Res Clin Oncol,2006,132(2):129-135.

[5] 贾立峰,李晓明.双氢青蒿素的抗肿瘤作用及机制[J].临床耳鼻咽喉头颈外科杂志,2013,27(18):1033-1036.

[6] 林芳,钱之玉,丁健,等.二氢青蒿素对人乳腺癌MCF-7细胞的体外抑制作用[J].中国新药杂志,2002,11(12):934-936.

[7] 刘世宜,李昕.低剂量长期砷暴露对HaCat细胞周期及周期蛋白的影响[J].中国公共卫生,2013,29(8):1190-1192.

[8] 陈卫强,戚好文,吴昌归,等.双氢青蒿素抗人肺腺癌A 549细胞生长的实验研究[J].中国肺癌杂志,2005,8(2):85-88.

[9] Hosoya K,Murahari S,Laio A,et al.Biological activity of dihydroartemisinin in canine osteosarcoma cell lines[J].Am J Vet Res,2008,69(4):519-526.

[10] Thoms HC,Dunlop MG,StarkLA.p38-mediated inactivation of cyclinD1/cyclin-dependent kinase 4 stimulates nucleolar translocation of RelA and apoptosis in colorectal cancer cells[J].Cancer Res,2007,67(4):1660-1669.

[11] Zuryń A,Litwiniec A,Gagat M,et al.The influence of arsenic trioxide on the cell cycle,apoptosis and expression of cyclin D1 in the Jurkat cell line[J].Acta Histochem,2014,116(8):1350-1358.

[12] Gopalakrishnan N,Saravanakumar M,Madankumar P,et al.Colocalization of β-catenin with Notch intracellular domain in colon cancer:a possible role of Notch1 signaling in activation of CyclinD1-mediated cell proliferation[J].Mol Cell Biochem,2014,396(1/2):281-293.

[13] Claudio L,Rosalia S,Bruna LS.Midregion PTHrP regulates Rip1and caspase expression in MDA-MB231 breast cancer cells[J].Breast Cancer Res Treat,2008,111(3):461-474.

[14] Nassar A,Lawson D,CotsonisG,et al. Survivin and caspase-3 expression in breast cancer:Correlation with prognostic parameters,proliferation,angiogenesis,and outcome[J].Appl Immunohistochem Mol Morphol,2008,16(3):113-129.

[15] Sui L,Dong Y,Ohno M,et al.Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors[J]. Int J Oncol,2002,21(2):315-320.

[16] 林鸿,文军,陈祥荣,等.双氢青蒿素对恶性胶质母细胞瘤细胞增殖与凋亡的影响[J].医药导报,2013,32(8):1003-1007.

双氢青蒿素对神经母细胞瘤细胞生长的抑制作用及其机制

Inhibitory effect of dihydroartemisinin on growth of neuroblastoma cells and its mechanism

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