Study on inhibitory effects and mechanism of silymarin on glioma <italic style="font-style: italic">in vivo</italic> and<italic style="font-style: italic"> in vitro</italic>

LIU Ming; LIU Xipeng; LI Chun; ZHEN Cheng; LIU Chunjiang; WANG Haiyang; GONG Jianqing

doi:10.6039/j.issn.1001-0408.2023.16.07

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Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro

更新时间：2023-08-24

- Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro
- ZHONGGUO YAOFANG Vol. 34, Issue 16, Pages: 1955-1960(2023)
- 作者机构：
  
  河北北方学院附属第一医院神经外科，河北张家口　075000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.16.07
  CLC： R965
- Published：30 August 2023，
  
  Received：08 February 2023，
  
  Revised：21 June 2023，
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刘明,刘熙鹏,李淳等.水飞蓟素对神经胶质瘤的体内外抑制作用及机制 ^Δ[J].中国药房,2023,34(16):1955-1960.

LIU Ming,LIU Xipeng,LI Chun,et al.Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro[J].ZHONGGUO YAOFANG,2023,34(16):1955-1960.
刘明,刘熙鹏,李淳等.水飞蓟素对神经胶质瘤的体内外抑制作用及机制 ^Δ[J].中国药房,2023,34(16):1955-1960. DOI： 10.6039/j.issn.1001-0408.2023.16.07.

LIU Ming,LIU Xipeng,LI Chun,et al.Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro[J].ZHONGGUO YAOFANG,2023,34(16):1955-1960. DOI： 10.6039/j.issn.1001-0408.2023.16.07.

摘要

目的

探讨水飞蓟素（SM）对神经胶质瘤的体内外抑制作用及潜在机制。

方法

将人神经胶质瘤细胞系U87随机分为对照组，低、中、高质量浓度SM组（50、100、200 μg/mL），蛋白激酶B（又称Akt）激活剂组（SC79 20 μmol/L），高质量浓度SM联合Akt激活剂组（SM 200 μg/mL+SC79 20 μmol/L）。经药物（对照组除外）处理后，检测各组细胞的光密度（OD）值、克隆形成率、凋亡率、增殖/凋亡相关蛋白[增殖细胞核抗原（PCNA）、B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3）]的表达情况和Akt/促分裂原活化的蛋白激酶（MAPK）信号通路相关蛋白[Akt、p38 MAPK、胞外信号调节激酶1/2（ERK1/2）]的磷酸化水平。于右侧腋窝内皮下注射U87细胞建立异种移植肿瘤裸鼠模型并将其分为对照组，低、中、高剂量SM组（25、50、100 mg/kg），Akt激活剂组（SC79 40 mg/kg）、高剂量SM联合Akt激活剂组（SM 100 mg/kg+SC79 40 mg/kg），每组5只。经药物（裸鼠对照组除外）干预后，称定其瘤体质量并计算瘤体体积。

结果

与对照组比较，SM各质量浓度组细胞的OD值，克隆形成率，PCNA、Bcl-2蛋白的表达水平，Akt、p38 MAPK、ERK1/2蛋白的磷酸化水平，以及裸鼠SM各剂量组裸鼠体内的瘤体质量及体积均显著降低/减小，细胞凋亡率和Bax、caspase-3蛋白的表达水平均显著升高，且均有剂量依赖性（

＜0.05）；Akt激活剂组上述指标的变化趋势与之相反（

＜0.05），且Akt激活剂可明显减弱高质量浓度/高剂量SM对神经胶质瘤的体内外抑制作用（

＜0.05）。

结论

SM可能通过抑制Akt/MAPK信号通路来促进U87细胞的凋亡，抑制其增殖、克隆形成以及异种移植瘤裸鼠体内肿瘤的生长。

Abstract

OBJECTIVE

To investigate the inhibitory effects of silymarin （SM） on glioma

in vivo

and

in vitro

and its potential mechanism.

METHODS

Human glioma cell line U87 cells were randomly divided into control group， SM low-concentration， SM medium-concentration and SM high-concentration groups （50， 100， 200 μg/mL）， protein kinase B （Akt） activator group （SC79 20 μmol/L）， high-concentration of SM combined with Akt activator group （SM 200 μg/mL+SC79 20 μmol/L）. After drug treatment （except for the control group）， optical density （OD） value， clone formation rate， apoptotic rate， the expressions of proliferation/apoptosis-related proteins [proliferating cell nuclear antigen （PCNA）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， caspase-3]， the phosphorylation levels of Akt/mitogen-activated protein kinase （MAPK） signaling pathway related proteins [Akt， p38 MAPK， extracellular signal-regulated kinase 1/2 （ERK1/2）] were detected in each group. The xenograft tumor model in nude mice was established by injecting U87 cells subcutaneously via the right armpit， and then divided into control group， SM low-dose， SM medium-dose and SM high-dose groups （25， 50， 100 mg/kg）， Akt activator group （SC79 40 mg/kg）， high-dose of SM combined with Akt activator group （SM 100 mg/kg+SC79 40 mg/kg）， with 5 mice in each group. After drug intervention （except for the control group of nude mice）， the tumor mass was weighed and the tumor volume was calculated.

RESULTS

Compared with control group， the OD values， clone formation rates， protein expressions of PCNA and Bcl-2， phosphorylation levels of Akt， p38 MAPK and ERK1/2 in SM groups， tumor mass and volume in nude mice of SM groups were all decreased significantly， while the apoptosis rates， protein expressions of Bax and caspase-3 were increased significantly， in a dose-dependent manner （

＜0.05）；the trend of changes in the above indicators in the Akt activator group was opposite （

＜0.05）， and Akt activator could significantly attenuate the inhibitory effect of high-concentration/high-dose SM on glioma

in vivo

and

in vitro （P

＜0.05）.

CONCLUSIONS

SM may promote the apoptosis of U87 cells， and inhibit its proliferation， clone formation and tumor growth in xenograft nude mice by inhibiting Akt/MAPK signaling pathway.

关键词

水飞蓟素神经胶质瘤蛋白激酶B/促分裂原活化的蛋白激酶信号通路细胞增殖克隆形成细胞凋亡

Keywords

gliomaprotein kinase B/mitogen-activated protein kinase signaling pathwayproliferationclone formationapoptosis

references

BANERJEE K，NÚÑEZ F J，HAASE S，et al. Current approaches for glioma gene therapy and virotherapy[J]. Front Mol Neurosci，2021，14：621831.

XIE Y，HE L Q，LUGANO R，et al. Key molecular alterations in endothelial cells in human glioblastoma unco-vered through single-cell RNA sequencing[J]. JCI Insight，2021，6（15）：e150861.

FU J Q，PENG J，TU G L. Knockdown MTDH inhibits glioma proliferation and migration and promotes apoptosis by downregulating MYBL2[J]. Mediators Inflamm，2022，2022：1706787.

WU W T，CHEN Y R，LU D H，et al. Silymarin modulates catabolic cytokine expression through Sirt1 and SOX9 in human articular chondrocytes[J]. J Orthop Surg Res，2021，16（1）：147.

唐寅，宋爱英，韩笑，等. 水飞蓟素通过Slit2调控非小细胞肺癌细胞增殖及凋亡的实验研究[J]. 中国医药导报，2022，19（28）：23-27，45.

王崇丞. BINP3介导的AIF核转位在水飞蓟宾诱导脑胶质瘤细胞自噬性死亡中的作用及机制[D]. 长春：吉林大学，2020.

MA Q F，WANG X Y，WANG H，et al. HMGN5 silencing suppresses cell biological progression via AKT/MAPK pathway in human glioblastoma cells[J]. Biomed Res Int，2020，2020：8610271.

李文海，梁军，王春梅，等. 水飞蓟素可通过MAPK信号转导通路促进肺腺癌A549细胞凋亡[J]. 第四军医大学学报，2008，29（5）：461-464.

KIM S H，CHOO G S，YOO E S，et al. Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis[J]. Oncol Lett，2021，21（6）：492.

宋建治，徐礼森，张晨，等. Akt激活剂SC79抑制地塞米松诱导成骨细胞凋亡和程序性坏死的作用机制[J]. 中国组织工程研究，2022，26（29）：4699-4703.

NI R J，GAO T H，WANG Y Y，et al. Chronic lithium treatment ameliorates ketamine-induced mania-like beha-vior via the PI3K-AKT signaling pathway[J]. Zool Res，2022，43（6）：989-1004.

ZHENG X Y，WANG Y G，WANG D X，et al. PSMC2 is overexpressed in glioma and promotes proliferation and anti-apoptosis of glioma cells[J]. World J Surg Oncol，2022，20（1）：84.

华金仁，刘荣芳，叶婷婷，等. 水飞蓟素诱导子宫内膜癌细胞凋亡的药理机制研究[J]. 临床合理用药杂志，2021，14（27）：4-7.

张健，马海，杨柳. 水飞蓟素抑制肝癌细胞系MHCC97侵袭及迁移[J]. 基础医学与临床，2019，39（12）：1741-1745.

RYU E，HA N Y，JUNG W，et al. Distinct motifs in ATAD5 C-terminal domain modulate PCNA unloading process[J]. Cells，2022，11（11）：1832.

薛淑一，李明春，苗青，等. 白头翁皂苷B4对肝癌细胞Huh-7及其荷瘤裸鼠肿瘤的抑制作用及机制研究[J]. 中国药房，2019，30（5）：601-607.

于传扬，赵菊芬，马荣，等. Mortalin通过PI3K/AKT通路对人神经胶质瘤细胞U87增殖迁移的影响[J]. 宁夏医科大学学报，2022，44（6）：597-602.

林兰，艾志宏. TRPV4通过调控MAPK/ERK信号通路促进卵巢癌细胞的增殖和迁移[J]. 现代肿瘤医学，2022，30（22）：4027-4032.

王彩丽，李夏红，陈玉. 南蛇藤提取物通过抑制PI3K/AKT信号通路对胃癌细胞转移和侵袭的影响[J]. 四川中医，2022，40（10）：62-66.

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⁰

Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro

DOI：10.6039/j.issn.1001-0408.2023.16.07

摘要

Abstract

关键词

Keywords

references