|Table of Contents|

Lycorine inhibits the proliferation of esophageal cancer cells through regulating G3BP1/TGF-β/Smad signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 04
Page:
603-609
Research Field:
Publishing date:

Info

Title:
Lycorine inhibits the proliferation of esophageal cancer cells through regulating G3BP1/TGF-β/Smad signaling pathway
Author(s):
REN Liping12 JIN Shaoju12 MA Yongchao2 XU Songtao23
1.Department of Pharmacy;3.Medical Department,Luohe Medical College,Henan Luohe 462002,China;2.Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose,Henan Luohe 462002,China.
Keywords:
lycorineG3BP1/TGF-β/Smad signaling pathwayesophageal cancercell proliferation
PACS:
R735.1
DOI:
10.3969/j.issn.1672-4992.2023.04.003
Abstract:
Objective:To explore the effect of lycorine on the proliferation of esophageal cancer cells and analyze its mechanism.Methods:The inhibition of cells was analyzed by cell counting kit-8 (CCK-8) method,and the levels of GTPase activating protein (SH3 domain) binding protein 1 (G3BP1),transforming growth factor-β1 (TGF-β1),p-Smad2/Smad2 and p-Smad3/Smad3 were analyzed by Western blot.After G3BP1 knockdown or overexpression,the inhibition rate of cell proliferation and the levels of G3BP1,TGF-β1,p-Smad2/Smad2 were observed.The tumorigenesis experiment in nude mice verified the effects of lycorine on the tumor weight,tumor volume and the levels of G3BP1,TGF-β1,p-Smad2/Smad2 in nude mice.Results:2~64 μmol/L lycorine inhibited the proliferation of ECA109 cells,and the IC50 of lycorine was (16.21±2.35) μmol/L for 48 hours.4,8,16 μmol/L lycorine could down-regulate the level of G3BP1,TGF-β1,p-Smad2/Smad2,p-Smad3/Smad3.Knocking down the expression of G3BP1 could obviously improve the inhibitory effect of lycorine on the proliferation of ECA109 cells,and promote lycorine to reduce the levels of G3BP1,TGF-β1 and p-Smad2/Smad2 (P<0.05).Up-regulating the expression of G3BP could obviously down-regulate the inhibitory effect of lycorine on the proliferation of ECA109 cells,and inhibit lycorine to decrease the levels of G3BP1,TGF-β1 and p-Smad2/Smad2 (P<0.05).In vivo experiments showed compared with the model control group,25,50 and 100 mg/kg lycorine could reduce the tumor volume and mass,and down-regulate the levels of G3BP1,TGF-β1 and p-Smad2/Smad2 (P<0.05).Conclusion:Lycorine can inhibit the proliferation of ECA109 cells,and has obvious antitumor effect on transplanted ECA109 cells of nude mice in vivo.Its mechanism is related to the regulation of G3BP1/TGF-β/Smad signaling pathway.

References:

[1] YAN S,XU J,LIU B,et al.Integrative bioinformatics analysis identifies LINC01614 as a potential prognostic signature in esophageal cancer[J].Transl Cancer Res,2021,10(4):1804-1812.
[2] MUKHOPADHYAY C,YANG C,XU L,et al.G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer[J].Nat Commun,2021,12(1):6662.
[3] ZHANG CH,LIU H,ZHAO WL,et al.G3BP1 promotes human breast cancer cell proliferation through coordinating with GSK-3β and stabilizing β-catenin[J].Acta Pharmacol Sin,2021,42(11):1900-1912.
[4] OMER A,BARRERA MC,MORAN JL,et al.G3BP1 controls the senescence-associated secretome and its impact on cancer progression[J].Nat Commun,2020,11(1):4979.
[5] ZHENG H,ZHAN Y,ZHANG Y,et al.Elevated expression of G3BP1 associates with YB1 and p-AKT and predicts poor prognosis in nonsmall cell lung cancer patients after surgical resection[J].Cancer Med,2019,8(16):6894-6903.
[6] LI Y,WANG J,ZHONG S,et al.Overexpression of G3BP1 facilitates the progression of colon cancer by activating β catenin signaling[J].Mol Med Rep,2020,22(5):4403-4411.
[7] ZHANG LN,ZHAO L,YAN XL,et al.Loss of G3BP1 suppresses proliferation,migration,and invasion of esophageal cancer cells via Wnt/β-catenin and PI3K/AKT signaling pathways[J].J Cell Physiol,2019,234(11):20469-20484.
[8] ZHANG B,ZHU Z,ZHANG X,et al.Inhibition of the proliferation,invasion,migration,and epithelial-mesenchymal transition of prostate cancer cells through the action of ATP1A2 on the TGF-β/Smad pathway[J].Transl Androl Urol,2022,11(1):53-66.
[9] MA X,GAO Y,CHEN Y,et al.M2-type macrophages induce tregs generation by activating the TGF-β/Smad signalling pathway to promote colorectal cancer development[J].Onco Targets Ther,2021,14:5391-5402.
[10] ZHENG M,NIU Y,BU J,et al.ESRP1 regulates alternative splicing of CARM1 to sensitize small cell lung cancer cells to chemotherapy by inhibiting TGF-β/Smad signaling[J].Aging (Albany NY),2021,13(3):3554-3572.
[11] GUAN L,ZHANG L,WANG T,et al.POM121 promotes proliferation and metastasis in non-small-cell lung cancer through TGF-β/SMAD and PI3K/AKT pathways[J].Cancer Biomark,2021,32(3):293-302.
[12] XU R,ZHOU XM,LI YS,et al.MicroRNA 181a promotes epithelial mesenchymal transition in esophageal squamous cell carcinoma via the TGF β/Smad pathway[J].Mol Med Rep,2021,23(5):316.
[13]HU M,YU Z,MEI P,et al.Lycorine induces autophagy-associated apoptosis by targeting MEK2 and enhances vemurafenib activity in colorectal cancer[J].Aging (Albany NY),2020,2(1):138-155.
[14]王利平,符鹏程,张华,等.吉非替尼联合氟尿嘧啶对食道癌细胞增殖的抑制作用[J].实用医学杂志,2011,27(3):378-381. WANG LP,FU PC,ZHANG H,et al.Inhibitory effect of gefitinib combined with fluorouracil on the proliferation of esophageal cancer cells[J].J Pract Med,2011,27(3):378-381.
[15] WANG L,LANG B,ZHOU Y,et al.Up-regulation of miR-663a inhibits the cancer stem cell-like properties of glioma via repressing the KDM2A-mediated TGF-β/SMAD signaling pathway[J].Cell Cycle,2021,20(19):1935-1952.
[16] DI Y,ZHAO HC,ZHU HC,et al.Ferroptosis is involved in the anti-tumor effect of lycorine in renal cell carcinoma cells[J].Oncol Lett,2021,22(5):781.
[17] MAO C,WANG X,LIU Y,et al.A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53[J].Cancer Res,2018,78(13):3484-3496.
[18] OMER A,BARRERA MC,MORAN JL,et al.G3BP1 controls the senescence-associated secretome and its impact on cancer progression[J].Nat Commun,2020,11(1):4979.
[19] WANG X,LAI Q,HE J,et al.LncRNA SNHG6 promotes proliferation,invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF1 and inducing EMT via regulation of ZEB1[J].Int J Med Sci,2019,16(1):51-59.
[20] XU R,ZHOU XM,LI YS,et al.MicroRNA 181a promotes epithelial mesenchymal transition in esophageal squamous cell carcinoma via the TGF β/Smad pathway[J].Mol Med Rep,2021,23(5):316-326.

Memo

Memo:
河南省高等学校重点科研项目(编号:22B310006);漯河医学高等专科学校创新创业发展能力提升工程项目(编号:2021LYZKJXM024,2020-LYZKYYB005)
Last Update: 1900-01-01