Baitouweng Tang Inhibits Growth of Esophageal Cancer Cells Through BUB1/STAT3 Signaling Pathway

YANG Hui; SHI Ning; CHEN Xiaowei; SONG Xuejie; SI Fuchun

doi:10.13422/j.cnki.syfjx.20240222

您当前的位置：

首页 >

文章列表页 >

Baitouweng Tang Inhibits Growth of Esophageal Cancer Cells Through BUB1/STAT3 Signaling Pathway

更新时间：2024-07-31

- Baitouweng Tang Inhibits Growth of Esophageal Cancer Cells Through BUB1/STAT3 Signaling Pathway
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 17, Pages: 10-17(2024)
- 作者机构：
  
  1.河南中医药大学中医学院，河南省中医方证信号传导重点实验室，河南省中医方证信号传导国际联合实验室，郑州 450046
  2.河南中医药大学医学院，郑州 450046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20240222
  CLC： R2-0;R22;R242;R285.5
- Published：05 September 2024，
  
  Published Online：08 December 2023，
  
  Received：20 October 2023，
- 稿件说明：
扫描看全文
杨晖,石宁,陈晓伟等.白头翁汤通过BUB1/STAT3信号通路抑制食管癌细胞生长[J].中国实验方剂学杂志,2024,30(17):10-17.

YANG Hui,SHI Ning,CHEN Xiaowei,et al.Baitouweng Tang Inhibits Growth of Esophageal Cancer Cells Through BUB1/STAT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(17):10-17.
杨晖,石宁,陈晓伟等.白头翁汤通过BUB1/STAT3信号通路抑制食管癌细胞生长[J].中国实验方剂学杂志,2024,30(17):10-17. DOI： 10.13422/j.cnki.syfjx.20240222.

YANG Hui,SHI Ning,CHEN Xiaowei,et al.Baitouweng Tang Inhibits Growth of Esophageal Cancer Cells Through BUB1/STAT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(17):10-17. DOI： 10.13422/j.cnki.syfjx.20240222.

摘要

目的

探讨白头翁汤通过调控苯并咪唑出芽抑制解除同源物蛋白1（BUB1）/信号转导及转录激活因子3（STAT3）信号通路抑制食管癌（EC）细胞生长的作用机制。

方法

运用基因芯片技术探讨EC组织和正常组织相关基因表达，筛选出差异表达基因，运用生物信息学技术对差异表达基因进行分析。用25、50、100、200、400、800 mg·L

-1

白头翁汤干预EC细胞，通过噻唑蓝（MTT）比色法检测EC9706细胞活力。用流式细胞术测定细胞周期和凋亡。通过实时荧光定量聚合酶链式反应（Real-time PCR）测定BUB1的表达。通过蛋白免疫印迹法（Western blot）测量BUB1、STAT3、磷酸化（p）-STAT3、细胞周期蛋白B1 （CCNB1）、细胞周期蛋白依赖性激酶1（CDK1）、B细胞淋巴瘤-2（Bcl-2）、胱天蛋白酶-3（Caspase-3）和胱天蛋白酶-9（Caspase-9）蛋白水平。用划痕和Trans

well侵袭实验测定细胞的迁移和侵袭能力。

结果

差异表达基因参与生物学过程、信号通路和网络构建主要与细胞有丝分裂相关，BUB1是关键的核心基因。与空白组比较，白头翁汤抑制BUB1表达（

0.05，

0.01）。体外实验表明，与空白组比较，白头翁汤能明显抑制EC细胞的生长（

0.05，

0.01）、迁移和侵袭（

0.05，

0.01），诱导细胞凋亡（

0.05，

0.01）和G

/M期升高（

0.01）。与空白组比较，白头翁汤处理后，EC细胞中Caspase-3、Caspase-9表达明显升高（

0.05，

0.01），Bcl-2、BUB1、CCNB1、CDK1表达明显降低（

0.05，

0.01）。STAT3信号通路也被发现在此过程中发挥着重要作用。

结论

白头翁汤可能通过下调BUB1介导STAT3信号通路抑制EC细胞的生长。

Abstract

Objective

To investigate the mechanism of Baitouweng Tang in inhibiting the growth of esophageal cancer （EC） cells by regulating budding uninhibited by benzimidazoles 1 （BUB1）/signal transducer and activator of transcription 3 （STAT3） signaling pathway.

Method

Gene chip technology was used to explore the differential gene expression between esophageal cancer tissues and normal tissues and identified differentially expressed genes. The differentially expressed genes were analyzed by bioinformatics methods. EC cells were treated with 25， 50， 100， 200， 400， 800 mg·L

-1

Baitouweng Tang. EC cell viability was detected by Thiazolyl Blue （MTT） colorimetry. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 was measured by real time quantitative polymerase chain reaction （Real-time PCR）. The protein levels of BUB1， STAT3， phosphorylated （p）-STAT3， Cyclin B1 （CCNB1）， cyclin-dependent kinase 1 （CDK1）， B-cell lymphoma-2 （Bcl-2）， cysteinyl aspartate-specific proteinase（Caspase）-3， and Caspase-9 were measured by Western blot. The migration and invasion abilities of the cells were measured by wound-healing and Transwell invasion assays.

Result

Differentially expressed genes were primarily involved in biological processes， signaling pathways， and network construction related to cell mitosis， with BUB1 identified as a key core gene. Compared with the control group， Baitouweng Tang inhibited BUB1 expression （

0.05，

0.01）.

In vitro

experiments showed that compared with the control group， Baitouweng Tang could significantly inhibit the growth （

0.05，

0.01）， migration and invasion （

0.05，

0.01） of EC cells， induce apoptosis （

0.05，

0.01）， and cause G

/M phase increase （

0.01）. After treatment with Baitouweng Tang， compared with the results in the control group， the expression of Caspase-3， and Caspase-9 in EC cells increased significantly （

0.05，

0.01）， while the expression of Bcl-2， BUB1， CCNB1， and CDK1 decreased significantly （

0.05，

0.01）. Moreover， the STAT3 signaling pathway was also found to play an important role in this process.

Conclusion

Baitouweng Tang may inhibit the growth of EC cells by downregulating BUB1 and mediating the STAT3 signaling pathway.

关键词

白头翁汤食管癌基因组学苯并咪唑出芽抑制解除同源物蛋白1（BUB1）信号转导及转录激活因子3（STAT3）信号通路

Keywords

Baitouweng Tangesophageal cancergenomicsbudding uninhibited by benzimidazoles 1 （BUB1）signal transducer and activator of transcription 3 （STAT3） signaling pathway

references

苏菲，贾立群，程志强，等.中医药干预食管癌前病变转癌相关研究进展［J］.中国实验方剂学杂志，2022，28（9）：242-247.

HUANG F L，YU S J.Esophageal cancer： Risk factors， genetic association， and treatment［J］.Asian J Surg，2018，41（3）：210-215.

刘茂伦，任珊，杨寒，等.基于Hedgehog信号通路探析白头翁汤抗结直肠癌HCT116细胞机制［J］.中国实验方剂学杂志，2023，29（8）：125-132.

刘锋. 《伤寒论》方剂对人食管癌TE-1、EC-1、EC109、EC9706细胞株生物学特性的影响［D］. 郑州：河南中医药大学，2018.

江始源. 《伤寒论》清热三方对人食管癌细胞增殖、凋亡和EGFR-PLC-γ1蛋白磷酸化水平的影响［D］. 郑州：河南中医药大学，2021.

SINGH P，PESENTI M E，MAFFINI S，et al.BUB1 and CENP-U， primed by CDK1， are the main PLK1 kinetochore receptors in mitosis［J］.Mol Cell，2021，81（1）：67-87.e9.

LI M， DUAN X， XIAO Y， et al. BUB1 is identified as a potential therapeutic target for pancreatic cancer treatment ［J］. Front Public Health， 2022， 6（10）：900853.

TONG H， WANG J， CHEN H， et al. Transcriptomic analysis of gene expression profiles of stomach carcinoma reveal abnormal expression of mitotic components ［J］. Life Sci， 2017， 170 （2）：41-49.

ZHU L J， PAN Y， CHEN X Y， et al. BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation ［J］. Oncol Lett， 2020，19（5）：3506-3512.

岳靖宇. 不同证候食管癌差异表达基因研究［D］. 郑州：河南中医学院，2012.

王朋辉，吴耀松，尚艺婉，等.启膈散联合顺铂对与成纤维细胞共培养的食管癌EC9706细胞生长的影响［J］.中医肿瘤学杂志，2020，2（3）：36-42.

LI L， JIANG D， ZHANG Q， et al. Integrative proteogenomic characterization of early esophageal cancer［J］. Nat Commun， 2023，14（1）：1666.

KWAK A W， LEE M J， LEE M H， et al. The 3-deoxysappanchalcone induces ROS-mediated apoptosis and cell cycle arrest via JNK/P38 MAPKs signaling pathway in human esophageal cancer cells ［J］. Phytomedicine， 2021，86（6）：153564.

KIM T， GARTNER A. BUB1 kinase in the regulation of mitosis ［J］. Anim Cells Syst （Seoul）， 2021，25（1）：1-10.

JOHNSON V L， SCOTT M I， HOLT S V， et al. Bub1 is required for kinetochore localization of BubR1， Cenp-E， Cenp-F and Mad2， and chromosome congression［J］. J Cell Sci， 2004， 117 （8）：1577-1589.

SEELEY T W，WANG L，ZHEN J Y. Phosphorylation of human MAD1 by the BUB1 kinase in vitro［J］.Biochem Biophys Res Commun，1999，257（2）：589-595.

KLEBIG C， KORINTH D， MERALDI P. BUB1 regulates chromosome segregation in a kinetochore-independent manner ［J］. J Cell Biol， 2009，185（5）：841-858.

HUANG Z，WANG S，WEI H，et al.Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways［J］.J Cell Mol Med，2021，25（17）：8442-8453.

YAO L L， CAO L Y， ZHANG H F， et al. Expression and clinical significance of Bub1 in esophageal squamous cancer［J］. J Mod Oncol， 2011，19（09）：1726-1730.

XUAN-QING C，XIANG-YU L V，SHI-JIA L.Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway［J］.J Ethnopharmacol，2021，265：113357.

GU X，MIAO Z，WANG Y，et al.New Baitouweng decoction combined with fecal microbiota transplantation alleviates DSS-induced colitis in rats by regulating gut microbiota metabolic homeostasis and the STAT3/NF-κB signaling pathway［J］.BMC Complement Med Ther，2022，22（1）：307.

PIAO X M，YOU C，BYUN Y J，et al. Prognostic value of BUB1 for predicting non-muscle-invasive bladder cancer progression［J］.Int J Mol Sci，2021，22（23）：12756.

JIN， XU H， LI W， et al. LINC00346 Acts as a Competing endogenous RNA regulating development of hepatocellular carcinoma via modulating CDK1/CCNB1 axis［J］. Front Bioeng Biotechnol， 2020， 18（8）：54.

LI M， SHANG H， WANG T， et al. Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducing CCNB1 expression［J］. World J Gastroenterol， 2021，27（10）：939-958.

SUNADA S，SAITO H，ZHANG D，et al.CDK1 inhibitor controls G2/M phase transition and reverses DNA damage sensitivity［J］.Biochem Biophys Res Commun，2021，550：56-61.

HUYNH J， CHAND A， GOUGH D， et al. Therapeutically exploiting STAT3 activity in cancer-using tissue repair as a road map［J］. Nat Rev Cancer， 2019，19（2）：82-96.

LIU Y L， YAN Z X， XIA Y， et al. Ligustrazine reverts anthracycline chemotherapy resistance of human breast cancer by inhibiting JAK2/STAT3 signaling and decreasing fibrinogen gamma chain （FGG） expression［J］. Am J Cancer Res， 2020，10（3）：939-952.

LIU Y，WANG X，ZENG S，et al.The natural polyphenol curcumin induces apoptosis by suppressing STAT3 signaling in esophageal squamous cell carcinoma［J］.J Exp Clin Cancer Res，2018，37（1）：303.

JIANG N，LIAO Y，WANG M，et al.BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway［J］.J Exp Clin Cancer Res，2021，40（1）：378.

陈斐然. BUB1在膀胱移行上皮癌中的表达与意义及BUB1磷酸化激活STAT3的机制研究［D］. 天津：天津医科大学， 2018.

XIAO Z J， LIU J， WANG S Q， et al. NFATc2 enhances tumor-initiating phenotypes through the NFATc2/SOX2/ALDH axis in lung adenocarcinoma ［J］. Elife， 2017，24（6）：26733.

SHEN H B， GU Z Q， JIAN K， et al. CXCR4-mediated STAT3 activation is essential for CXCL12-induced cell invasion in bladder cancer ［J］. Tumour Biol， 2013，34 （3）：1839-1845.

RESETCA D，HAFTCHENARY S，GUNNING P T，et al.Changes in signal transducer and activator of transcription 3 （STAT3） dynamics induced by complexation with pharmacological inhibitors of Src homology 2 （SH2） domain dimerization［J］.J Biol Chem，2014，289（47）：32538-32547.

ROBKER R L，WATSON L N，ROBERTSON S A，et al.Identification of sites of STAT3 action in the female reproductive tract through conditional gene deletion［J］.PLoS One，2014，9（7）：e101182.

ZHANG C H， GUO F L， XU G L， et al. STAT3 activation mediates epithelial-to-mesenchymal transition in human hepatocellular carcinoma cells［J］. Hepato-gastroenterology， 2014，61（132）：1082-1089.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Chinese Medicine Regulates Signaling Pathways Related to Esophageal Cancer： A Review

Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention：A Review

Macroscopic Clinical Medication Pattern of Traditional Chinese Medicine for Esophageal Cancer in Recent Ten Years Based on Data Mining

Baitouweng Tang Suppresses Colorectal Cancer HCT116 Cells by Regulating Hedgehog Signaling Pathway

Related Author

LI Shanshan

WEI Dandan

PEI Junwen

WANG Hongling

JIANG shiqing

XU Mingyao

LI Liqun

LIU Xin

Related Institution

Henan University of Chinese Medicine

The Third Affiliated Hospital of Henan University of Chinese Medicine

Henan Cancer Hospital

The First Affiliated Hospital of Henan University of Chinese Medicine

Graduate School of Guangxi University of Traditional Chinese Medicine（TCM）

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰