白花蛇舌草对A549肺癌干细胞增殖、凋亡及细胞周期的影响
|
摘要
目的探讨白花蛇舌草对肺癌干细胞增殖、凋亡及细胞周期的影响。方法诱导培养A549肺癌干细胞球,免疫组织化学检测Sox2、Oct4表达,CCK-8检测白花蛇舌草提取物对细胞增殖的影响,流式细胞检测白花蛇舌草提取物对细胞凋亡率及细胞周期的影响。结果 A549肺癌干细胞中的CD133阳性率(70.483 30±0.092 92)%,A549细胞中仅为(5.056 70±0.185 83)%。Sox2、Oct4表达在A549细胞及A549肺癌干细胞中均呈阳性,主要在细胞质,在A549肺癌干细胞中染色强度更强。白花蛇舌草能抑制A549肺癌干细胞增殖,且呈时间依赖性(P<0.05);白花蛇舌草使A549肺癌干细胞的细胞凋亡率增加(P<0.05),G_1期细胞数目增多(P<0.05)。结论白花蛇舌草能抑制A549肺癌干细胞增殖,促进细胞凋亡,阻滞细胞周期于G_1期。
Objective To study the effect of hedyotis diffusa on proliferation,apoptosis and cell cycle of lung cancer stem cells.Methods The A549 lung cancer stem cell spheves were cultured and induced.The expressions of Sox2 and Oct4 were detected by immunohistochemistry.The CCK8 assay was used to detect the effect of hedyotis diffusa extract on cell proliferation.The flow cytometry was used to detect the effect of hedyotis diffusa extract on the apoptosis rate and cell cycle.Results The CD133 positive rate of A549 lung cancer stem cells was(70.483 30±0.092 92)%,which in A549 cells was only(5.056 70±0.185 83)%.Sox2 and Oct4 all showed positive expression in A549 cells and A549 lung cancer stem cells,which was mainly in cytoplasma.The staining intensity was stronger in A549 lung cancer stem cells.Hedyotis diffusa could inhibit the proliferation of A549 lung cancer stem cells,moreover which showed the time dependence(P<0.05).Hedyotis diffusa increased the cellular apoptosis rate of A549 lung cancer stem cells(P<0.05)and the number of cells in G_1 stage(P<0.05).Conclusion Hedyotis diffusa can inhibit the proliferation of A549 lung cancer stem cells,promote the cell apoptosis and block the cell cycle at G1 stage.
Objective To study the effect of hedyotis diffusa on proliferation,apoptosis and cell cycle of lung cancer stem cells.Methods The A549 lung cancer stem cell spheves were cultured and induced.The expressions of Sox2 and Oct4 were detected by immunohistochemistry.The CCK8 assay was used to detect the effect of hedyotis diffusa extract on cell proliferation.The flow cytometry was used to detect the effect of hedyotis diffusa extract on the apoptosis rate and cell cycle.Results The CD133 positive rate of A549 lung cancer stem cells was(70.483 30±0.092 92)%,which in A549 cells was only(5.056 70±0.185 83)%.Sox2 and Oct4 all showed positive expression in A549 cells and A549 lung cancer stem cells,which was mainly in cytoplasma.The staining intensity was stronger in A549 lung cancer stem cells.Hedyotis diffusa could inhibit the proliferation of A549 lung cancer stem cells,moreover which showed the time dependence(P<0.05).Hedyotis diffusa increased the cellular apoptosis rate of A549 lung cancer stem cells(P<0.05)and the number of cells in G_1 stage(P<0.05).Conclusion Hedyotis diffusa can inhibit the proliferation of A549 lung cancer stem cells,promote the cell apoptosis and block the cell cycle at G1 stage.
引文
[1]陈万青,孙可欣,郑荣寿,等.2014年中国部分地区恶性肿瘤发病和死亡分析[J].中国肿瘤,2018,27(1):1-14.
[2]凌昌全.中医药在防治肿瘤中的作用和地位[J].中国中西医结合杂志,2007,27(5):390-391.
[3]马雪曼,张培彤.CD133肿瘤干细胞标志物在肺癌中的应用进展[J].中国肿瘤,2014,23(3):224-227.
[4]王耀焓,张培彤.肺癌干细胞标志物研究现状[J].中国肿瘤,2015,24(8):671-676.
[5]SARVI S,MACKINNON A C,AVLONITIS N,et al.CD133+cancer stem-like cells in small cell lung cancer are highly tumorigenic and che-moresistant but sensitive to a novel neuropeptide antagonist[J].Cancer Res,2014,74(5):1554-1565.
[6]TAN Y,CHEN B,XU W,et al.Clinicopathological significance of CD133in lung cancer:a meta-analysis[J].Mol Clin Oncol,2014,2(1):111-115.
[7]ZHU J Y,YANG X,CHEN Y,et al.Curcumin suppresses lung cancer stem cells via inhibiting wnt/β-catenin and sonic hedgehog pathways[J].Phyt Res,2017,31(4):680-688.
[8]ZAKARIA N,MOHD YUSOFF N,ZAKARIA Z,et al.Inhibition of NF-κB signaling reduces the stemness characteristics of lung cancer stem cells[J].Front Oncol,2018,8:166.
[9]杨明,陈静,易娟,等.纳米雄黄对肺癌A549细胞及其肿瘤干细胞的凋亡诱导作用[J].中药药理与临床,2010,26(6):39.
[10]LIU L,ZHANG L,YANG L,et al.Anti-CD47antibody as a targeted therapeutic agent for human lung cancer and cancer stem cells[J].Front Immunol,2017,404(8):3389-3398.
[11]SHIOTANI B,KOBAYASHI M,WATANABE M,et al.Involvement of the ATR and ATM dependent checkpoint responses in the cell cycle arrest evoked by pierisin-1[J].Mol Cancer Res,2006,4(2):125-133.
[12]杨栋,张培彤.肺癌干细胞研究进展[J].中国肿瘤,2015,24(7):574-580.
[13]苏婉,徐振晔.历代中医医籍中肺癌相关文献概述[J].中医文献杂志,2010,28(1):53-55.
[14]石文静,谭佳妮,沈卫星,等.清热解毒与以毒攻毒治法在肿瘤治疗中的比较研究[J].时珍国医国药,2017,28(9):2184-2186.
[15]马超,朴惠善.白花蛇舌草的研究进展[J].时珍国医国药,2006,17(2):269-270.
[16]于亮,王芳,郭琪,等.白花蛇舌草的化学成分及其药理活性研究进展[J].沈阳药科大学学报,2017,34(12):1104-1114.
[2]凌昌全.中医药在防治肿瘤中的作用和地位[J].中国中西医结合杂志,2007,27(5):390-391.
[3]马雪曼,张培彤.CD133肿瘤干细胞标志物在肺癌中的应用进展[J].中国肿瘤,2014,23(3):224-227.
[4]王耀焓,张培彤.肺癌干细胞标志物研究现状[J].中国肿瘤,2015,24(8):671-676.
[5]SARVI S,MACKINNON A C,AVLONITIS N,et al.CD133+cancer stem-like cells in small cell lung cancer are highly tumorigenic and che-moresistant but sensitive to a novel neuropeptide antagonist[J].Cancer Res,2014,74(5):1554-1565.
[6]TAN Y,CHEN B,XU W,et al.Clinicopathological significance of CD133in lung cancer:a meta-analysis[J].Mol Clin Oncol,2014,2(1):111-115.
[7]ZHU J Y,YANG X,CHEN Y,et al.Curcumin suppresses lung cancer stem cells via inhibiting wnt/β-catenin and sonic hedgehog pathways[J].Phyt Res,2017,31(4):680-688.
[8]ZAKARIA N,MOHD YUSOFF N,ZAKARIA Z,et al.Inhibition of NF-κB signaling reduces the stemness characteristics of lung cancer stem cells[J].Front Oncol,2018,8:166.
[9]杨明,陈静,易娟,等.纳米雄黄对肺癌A549细胞及其肿瘤干细胞的凋亡诱导作用[J].中药药理与临床,2010,26(6):39.
[10]LIU L,ZHANG L,YANG L,et al.Anti-CD47antibody as a targeted therapeutic agent for human lung cancer and cancer stem cells[J].Front Immunol,2017,404(8):3389-3398.
[11]SHIOTANI B,KOBAYASHI M,WATANABE M,et al.Involvement of the ATR and ATM dependent checkpoint responses in the cell cycle arrest evoked by pierisin-1[J].Mol Cancer Res,2006,4(2):125-133.
[12]杨栋,张培彤.肺癌干细胞研究进展[J].中国肿瘤,2015,24(7):574-580.
[13]苏婉,徐振晔.历代中医医籍中肺癌相关文献概述[J].中医文献杂志,2010,28(1):53-55.
[14]石文静,谭佳妮,沈卫星,等.清热解毒与以毒攻毒治法在肿瘤治疗中的比较研究[J].时珍国医国药,2017,28(9):2184-2186.
[15]马超,朴惠善.白花蛇舌草的研究进展[J].时珍国医国药,2006,17(2):269-270.
[16]于亮,王芳,郭琪,等.白花蛇舌草的化学成分及其药理活性研究进展[J].沈阳药科大学学报,2017,34(12):1104-1114.