白术内酯Ⅰ抑制卵巢癌SK-OV-3与OVCAR-3细胞增殖的作用机制研究
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- 英文论文题名：The Mechanism and Proliferation Inhibitory Effect of Atractylenolide Ⅰ on SK-OV-3 and OVCAR-3 Ovarian Cancer Cell
- 论文作者：龙方懿 ; 贾萍 ; 王华飞 ; 卿轶 ; 何梦婕 ; 王晓丽
- 英文论文作者：LONG Fang-yi ; JIA Ping ; WANG Hua-fei ; QING Yi ; HE Meng-jie ; WANG Xiao-li ; Department of Pharmacy ; Maternal and Child Health Hospital of Sichuan
- 年：2016
- 作者机构：四川省妇幼保健院药学部;
- 论文关键词：白术内酯Ⅰ ; 细胞增殖 ; 细胞周期 ; PI3K/AKT ; 卵巢癌
- 英文论文关键词：Atractylenolide Ⅰ ; Proliferation ; Cell cycle ; PI3K/AKT ; Ovarian cancer
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：中文
- 分类号：R285
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：7
- 文件大小：979k
- 原文格式：O
- 会议级别：全国
摘要
目的探讨白术内酯Ⅰ抑制卵巢癌SK-OV-3与OVCAR-3细胞增殖的作用及其分子机制。方法:MTT实验检测不同浓度白术内酯Ⅰ作用人卵巢癌SK-OV-3与OVCAR-3细胞24h、48h与72h后,白术内酯Ⅰ对卵巢癌细胞增殖的影响;流式细胞技术与PI染色检测白术内酯Ⅰ对卵巢癌SK-OV-3与OVCAR-3细胞周期的影响,ELISA实验检测白术内酯Ⅰ对卵巢癌SK-OV-3与OVCAR-3细胞cyclin D1与CDK1表达的影响;Western Blot测定白术内酯Ⅰ对卵巢癌SK-OV-3与OVCAR-3细胞PI3K/AKT信号通路的影响。结果:白术内酯Ⅰ可显著抑制SK-OV-3与OVCAR-3细胞增殖,且白术内酯Ⅰ对SK-OV-3与OVCAR-3细胞的增殖抑制作用具有浓度和时间依赖性;此外,白术内酯Ⅰ还可显著降低SK-OV-3与OVCAR-3细胞的S期细胞比例,增加G2/M期细胞比例,且白术内酯Ⅰ对SK-OV-3与OVCAR-3细胞周期的调控与其抑制CDKl的表达有关;Western Blot实验进一步探讨了白术内酯Ⅰ抑制细胞增殖和调控细胞周期与PI3K/AKT信号通路有关。结论:白术内酯Ⅰ可通过PI3K/AKT途径下调卵巢癌SK-OV-3与OVCAR-3细胞CDKl的表达,从而使细胞阻滞于G2/M期,进而发挥肿瘤细胞增殖抑制作用。
OBJECTIVE To investigate the mechanisms and proliferation inhibitory effects of atractylenolide Ⅰ on SK-OV-3and OVCAR-3 ovarian cancer cell.METHODS SK-OV-3 and OVCAR-3 cells were treated with atractylenolide Ⅰ at various concentrations(0,5,10,20,40,80 and 160 μM)for different time(24,48,and 72 h),and the changes in proliferation were detected by MTT assay.The cell cycles were measured by flow cytometry and the expressions of cyclin D1 and CDK1 were detected by ELISA assay.Western Blot was then applied to investigate the effects of atractylenolide Ⅰ on PI3K/AKT signaling pathway in SK-OV-3 and OVCAR-3 cells.RESULTS Atractylenolide Ⅰ could significantly inhibit the proliferation of SK-OV-3and OVCAR-3 cells,and its inhibitory effects were concentration and time dependent.In addition,atractylenolide Ⅰ could also significantly reduce the proportion of cells in S phase,and increase the proportion of cells in G2/M phase,and these effects were associated with the down-regulation of CDK1.The results of Western Blot indicated that PI3K/AKT signaling pathway was involved in the inhibitory effects of atractylenolide Ⅰ on proliferation and cell cycle.CONCLUSION Atractylenolide Ⅰ could down-regulate the expression of CDK1 in ovarian cancer SK-OV-3 and OVCAR-3 cells through PI3K/AKT pathway,which led to cell cycle arrest in G2/M phase,and played an important role in proliferation inhibition of tumor cells.
OBJECTIVE To investigate the mechanisms and proliferation inhibitory effects of atractylenolide Ⅰ on SK-OV-3and OVCAR-3 ovarian cancer cell.METHODS SK-OV-3 and OVCAR-3 cells were treated with atractylenolide Ⅰ at various concentrations(0,5,10,20,40,80 and 160 μM)for different time(24,48,and 72 h),and the changes in proliferation were detected by MTT assay.The cell cycles were measured by flow cytometry and the expressions of cyclin D1 and CDK1 were detected by ELISA assay.Western Blot was then applied to investigate the effects of atractylenolide Ⅰ on PI3K/AKT signaling pathway in SK-OV-3 and OVCAR-3 cells.RESULTS Atractylenolide Ⅰ could significantly inhibit the proliferation of SK-OV-3and OVCAR-3 cells,and its inhibitory effects were concentration and time dependent.In addition,atractylenolide Ⅰ could also significantly reduce the proportion of cells in S phase,and increase the proportion of cells in G2/M phase,and these effects were associated with the down-regulation of CDK1.The results of Western Blot indicated that PI3K/AKT signaling pathway was involved in the inhibitory effects of atractylenolide Ⅰ on proliferation and cell cycle.CONCLUSION Atractylenolide Ⅰ could down-regulate the expression of CDK1 in ovarian cancer SK-OV-3 and OVCAR-3 cells through PI3K/AKT pathway,which led to cell cycle arrest in G2/M phase,and played an important role in proliferation inhibition of tumor cells.
引文
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[2]HU Y J,XUE F X.The progress in anti-vascular target therapy in ovarian cancer[J].J Int Obstet Gynecol,2010,37(4):271-3.
[3]HUANG H L,LIN T W,HUANG Y L et al.Induction of apoptosis and differentiation by atractylenolide-1 isolated from Atractylodes macrocephala in human leukemia cells[J].Bioorg Med Chem Lett.2016,26(8):1905-9.
[4]YU R,YU B X,CHEN J F et al.Anti-tumor effects of Atractylenolide I on bladder cancer cells[J].J Exp Clin Cancer Res.2016,35:40.
[5]YE Y,CHAO X J,WU J F et al.ERK/GSK3βsignaling is involved in atractylenolide I-induced apoptosis and cell cycle arrest in melanoma cells[J].Oncol Rep.2015,34(3):1543-8.
[6]HUANG J M,ZHANG G N,SHI Y et al.Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4/MyD88-dependent pathway[J].Sci Rep.2014,4:3840.
[7]ZHONG Z,YEOW W S,ZOU C,et al.Cyclin D1/cyclin-dependent kinase 4 interacts with filamin A and affects the migration and invasionpotential of breast cancer cells[J].Cancer Res,2010,70(5):2105-14.
[8]HUANG W W,TSAI S C,PENG S F et al.Kaempferol induces autophagy through AMPK.and AKT signaling molecules and causes G2/M arrest via downregulation of CDK1/cyclin B in SK-HEP-1 human hepatic cancer cells.Int J Oncol.2013,42(6):2069-77.
[9]PRASAD R,VAID M,KATIYAR S K.Grape Proanthocyanidin Inhibit Pancreatic Cancer Cell Growth In Vitro and In Vivo through Induction of Apoptosis and by Targeting the PI3K/Akt Pathway[J].PLoS One,2012,7(8):e43064.
[10]WANG T E,WANG Y K,JIN J et al.A novel derivative of quinazoline,WYK431 induces G2/M phase arrest and apoptosis in human gastric cancer BGC823 cells through the PI3K/Akt pathway.Int J Oncol.2014,45(2):771-81.