[1]韩福新,马善波,张 蕊.白花丹素调节MEK/ERK通路增加脑胶质瘤U87细胞对替莫唑胺的敏感性研究[J].陕西医学杂志,2021,50(11):1327-1332.[doi:DOI:10.3969/j.issn.1000-7377.2021.11.002]
　HAN Fuxin,MA Shanbo,ZHANG Rui.Plumbagin modulates MEK/ERK pathway to increase sensitivity of glioma U87 cells to temozolomide[J].,2021,50(11):1327-1332.[doi:DOI:10.3969/j.issn.1000-7377.2021.11.002]
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白花丹素调节MEK/ERK通路增加脑胶质瘤U87细胞对替莫唑胺的敏感性研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年11期
页码:
1327-1332
栏目:
基础研究
出版日期:
2021-11-05

文章信息/Info

Title:
Plumbagin modulates MEK/ERK pathway to increase sensitivity of glioma U87 cells to temozolomide
作者:
韩福新1; 马善波2; 张 蕊2
(1.西安市人民医院 西安市第四医院,陕西 西安710004; 2.空军军医大学西京医院,陕西 西安710032)
Author(s):
HAN Fuxin; MA Shanbo; ZHANG Rui
(Xi'an People's Hospital,Xi'an 710004,China)
关键词:
白花丹素;  MEK/ERK通路;  脑胶质瘤;  替莫唑胺;  U87细胞;  化疗敏感性
Keywords:
Plumbagin;  MEK/ERK pathway;  Glioma;  Temozolomide;  U87 cells;  Chemosensitivity
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2021.11.002
文献标志码:
A
摘要:
目的:研究白花丹素联合替莫唑胺对脑胶质瘤U87细胞的增殖、迁移和侵袭抑制作用及对U87细胞MEK/ERK通路的调节作用。方法:分别设置空白对照组、替莫唑胺组、白花丹素组及白花丹素联合替莫唑胺组,白花丹素组加入终浓度为10 μmol/L的白花丹素,替莫唑胺组加入终浓度为100 μmol/L的替莫唑胺,白花丹素联合替莫唑胺组加入白花丹素(10 μmol/L)及替莫唑胺(100 μmol/L)培养U87细胞,细胞计数试剂(CCK)-8法检测24、48、72 h各组U87细胞增殖抑制率,划痕实验检测U87细胞迁移率,Transwell检测U87细胞侵袭能力,原位末端转移酶标记技术(TUNEL)法检测U87细胞凋亡率,实时定量聚合酶链式反应(RTq-PCR)检测U87细胞MEK及ERK mRNA水平,免疫印迹法(Western blot)检测U87细胞MEK及ERK蛋白水平。结果:与空白对照组比较,白花丹素组、替莫唑胺组及白花丹素联合替莫唑胺组U87细胞迁移率、侵袭细胞数、MEK及ERK mRNA及蛋白水平均显著降低(均P<0.05),而U87细胞凋亡率则显著升高(P<0.05); 与白花丹素组及替莫唑胺组比较,白花丹素联合替莫唑胺组U87细胞迁移率、侵袭细胞数、MEK及ERK mRNA及蛋白水平均显著降低(均P<0.05),U87细胞24、48、72 h增殖抑制率及凋亡率显著升高(均P<0.05)。结论:白花丹素能够增强U87细胞对替莫唑胺的敏感性,显著抑制U87细胞的增殖、迁移和侵袭,诱导U87细胞凋亡,其机制可能与调节MEK/ERK通路有关。
Abstract:
Objective:To study the inhibitory effects of plumbagin combined with temozolomide on the proliferation,migration and invasion of U87 glioma cells and the regulation of the MEK/ERK pathway in U87 cells.Methods:The blank control group,temozolomide group,plumbagin group and plumbagin combined with temozolomide group were set up respectively.The plumbagin group was added with plumbagin at a final concentration of 10 μmol/L,and the temozolomide group was added with temozolomide at a final concentration of 100 μmol/L.In the plumbagin combined with temozolomide group,plumbagin(10 μmol/L)and temozolomide(100 μmol/L)were added to culture U87 cells.The CCK-8 method was used to detect the proliferation inhibition rate of U87 cells in at 24,48 and 72 hours.The scratch test was used to detect the migration rate of U87 cells.Transwell test was used to detect invasion ability of U87 cells.TUNEL method was used to detect apoptosis rate of U87 cells.Real-time quantitative polymerase chain reaction(RTq-PCR)was used to detect MEK and ERK mRNA levels of U87 cells.Western blot was used to detect MEK and ERK protein levels of U87 cells.Results:Compared with the blank control group,migration rate of U87 cells,number of invasion cells,levels of MEK and ERK mRNAs and proteins in plumbagin group,temozolomide group and plumbagin combined with temozolomide group were significantly reduced(all P<0.05),while apoptosis rate of U87 cells was significantly increased(P<0.05).Compared with plumbagin and temozolomide group,migration rate of U87 cell,number of invasive cells,levels of MEK and ERK mRNAs and proteins in plumbagin combined with temozolomide group were significantly reduced(all P<0.05),the proliferation inhibition rate and apoptosis rate of U87 cells at 24,48,and 72 hours were significantly increased(all P<0.05).Conclusion:Plumbagin can enhance the sensitivity of U87 cells to temozolomide,significantly inhibit the proliferation,migration and invasion of U87 cells,and induce apoptosis of U87 cell.The mechanism may be related to the regulation of the MEK/ERK pathway.

参考文献/References:

[1] Digregorio M,Lombard A,Lumapat PN,et al.Relevance of translation initiation in diffuse glioma biology and its therapeutic potential[J].Cells,2019,8(12):1542.
[2] 徐泽彪,胡珍渊,方永军,等.胶质瘤中环状RNA has-circ-0037251水平检测及临床意义[J].陕西医学杂志,2021,50(2):229-232.
[3] 李卫峰.Ki-67、Bcl-2、Bax和Caspase-3在脑胶质瘤组织中的表达及临床意义[J].陕西医学杂志,2018,47(11):1377-1399.
[4] Khaw AK,Sameni S,Venkatesan S,et al.Plumbagin alters telomere dynamics,induces DNA damage and cell death in human brain tumour cells[J].Mutat Res Genet Toxicol Environ Mutagen,2015,793(1):86-95.
[5] Liu X,Cai W,Niu M,et al.Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1[J].J Neurooncol,2015,121(3):469-477.
[6] Ramaswamy P,Goswami K,Dalavaikodihalli N,et al.TNF-α mediated MEK-ERK signaling in invasion with putative network involving NF-κB and STAT-6:A new perspective in glioma[J].Cell Biol Int,2019,43(11):1257-1266.
[7] Ramaswamy P,Nanjaiah ND,Borkotokey M.Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix:Possible implication on migration and proliferation[J].Ann Neurosci,2019,26(2):52-56.
[8] 赵海康,潘 力,张 亮,等.替莫唑胺通过TFRC抑制U87胶质瘤细胞增殖和侵袭[J].中国临床神经外科杂志,2019,24(11):685-689.
[9] 高 伟,钟仕洋,马 云,等.不同浓度白花丹素对骨肉瘤细胞MG-63凋亡迁移、基质金属蛋白酶及Bcl-2、Bax、Ezrin蛋白表达的影响[J].现代生物医学进展,2021,21(2):201-204.
[10] 韩 蕾,周俊林.影像学评价脑胶质瘤动物实验的研究进展[J].临床放射学杂志,2020,39(7):1448-1450.
[11] 江 涛.2018年脑胶质瘤进展与展望[J].中华医学信息导报,2019,34(2):16.
[12] 刘昌明,黄香尘,杜 斌.白花丹素调控ROS抑制NLRP3炎症小体减轻IgA肾损伤机制的实验研究[J].中国临床解剖学杂志,2020,38(3):71-76.
[13] 曾 慧,梅 劼.白花丹素通过抑制上皮间质转化对卵巢癌细胞SKOV3侵袭和迁移能力的影响[J].中国临床药理学杂志,2020,36(3):301-304.
[14] 雷静文,宋丽华,张晓京,等.白花丹素改善高脂饮食小鼠肝脏脂代谢并降低糖异生的研究[J].中国现代应用药学,2020,37(22):2720-2726.
[15] 柴 昌,宋来君,韩双印,等.SOX2和miR-200b对胶质瘤临床病理和预后的影响及其相互关系[J].中华神经医学杂志,2014,13(10):984-989.
[16] Niu M,Cai W,Liu H,et al.Plumbagin inhibits growth of gliomas in vivo via suppression of FOXM1 expression[J].J Pharmacol Sci,2015,128(3):131-136.
[17] Chen G,Yue Y,Qin J,et al.Plumbagin suppresses the migration and invasion of glioma cells via downregulation of MMP-2/9 expression and inaction of PI3K/Akt signaling pathway in vitro[J].J Pharmacol Sci,2017,134(1):59-67.
[18] 孙 关,桂群峰,万政强,等.MiR-15b对人脑胶质瘤细胞株A172增殖和凋亡的影响[J].中华神经外科杂志,2015,31(11):1161-1165.
[19] 王 帆,陈锋龙,胡伟鹏,等.Mig-7通过MEK/ERK信号通路抑制胶质瘤U251侵袭及血管生成拟态[J].南方医科大学学报,2019,39(5):68-73.
[20] 赵永顺,吴春明,董 斌,等.榄香烯抑制Raf/MEK/ERK信号通路诱导人源胶质瘤U87细胞凋亡[J].实用药物与临床,2011,14(5):365-367.

备注/Memo

备注/Memo:
基金项目:陕西省自然科学基础研究计划项目(2020JM-701)
更新日期/Last Update: 2021-11-05