|Table of Contents|

Effects of Sinomenine regulating CXCR4-STAT3 axis on proliferation,migration and angiogenic mimicry of ovarian cancer A2780 cells

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

Issue:
2024 16
Page:
2944-2951
Research Field:
Publishing date:

Info

Title:
Effects of Sinomenine regulating CXCR4-STAT3 axis on proliferation,migration and angiogenic mimicry of ovarian cancer A2780 cells
Author(s):
YAN Zhenyu1; GUO Meng2; YANG Ran3; SU Bo1; ZHANG Haiyan4
1.Department of Pathology;2.Department of Oncology;3.Department of Gynaecology，Nanyang Central Hospital,Henan Nanyang 473000,China;4.Pathology Department,the First Affiliated Hospital of Nanyang Medical College,Henan Nanyang 473000,China.
Keywords:
Sinomenine; CXC chemokine receptor 4-signal transduction and transcriptional activator 3 axis; ovarian cancer cells; proliferation; migration; angiogenic mimicry
PACS:
R737.31
DOI:
10.3969/j.issn.1672-4992.2024.16.004
Abstract:
Objective:To investigate the influences and mechanism of Sinomenine on the proliferation,migration and angiogenesis mimicry of ovarian cancer cells.Methods:A2780 cells were treated with Sinomenine at different concentrations (0,0.25,0.50,1.0,2.0,4.0,8.0 mmol/L) for 24 and 48 h respectively,and the cell viability was detected by CCK-8 method.A2780 cells were randomly separated into Control group,CXCR4 activator stromal cell-derived factor-1(SDF-1)(SDF-1,100 ng/mL) group,CXCR4 inhibitor Plerixafor(Plerixafor,500 ng/mL) group,Sinomenine (1.0 mmol/L) group,and Sinomenine+SDF-1 (1.0 mmol/L Sinomenine+100 ng/mL SDF-1) group.The proliferation,migration and invasion of A2780 cells were detected,respectively.The effect of Sinomenine on angiogenesis mimicry was detected by in vitro angiogenesis mimicry formation assay.Western blot was applied to detect the protein expression of vascular endothelial growth factor (VEGF),epithelial cell kinase (EphA2),matrix metalloproteinase 9 (MMP-9),MMP-2,CXC chemokine receptor 4 (CXCR4),signal transduction and transcriptional activator 3 (STAT3),phosphorylated STAT3 (p-STAT3).Results:Sinomenine could effectively inhibit the proliferation of A2780 cells in a concentration-dependent manner.Sinomenine could greatly inhibit the migration,invasion and angiogenesis mimicry formation of A2780 cells,down-regulate the expression of angiogenesis mimicry marker proteins VEGF,EphA2,MMP-9,MMP-2,and inhibit the expression of CXCR4 and p-STAT3 (P＜0.05),and this inhibitory effect of Sinomenine could be attenuated by CXCR4 activators.Conclusion:Sinomenine may inhibit proliferation,migration,invasion and angiogenic mimicry formation of ovarian cancer cells by inhibiting CXCR4-STAT3 axis.

References:

［1］ TIAN X,SI Q,LIU M,et al.Advance in vasculogenic mimicry in ovarian cancer (review)［J］.Oncol Lett,2023,26(4):456-471.
［2］ 梁军,邢慧敏,吴小华,等.人卵巢癌SKOV3细胞筛选获得的肿瘤干细胞样细胞在血管生成拟态形成中的作用［J］.南方医科大学学报,2019,39(9):1065-1070. LIANG J,XING HM,WU XH,et al.The role of tumor stem-like cells derived from SKOV3 cell screening in the formation of angiogenic mimicry ［J］.J South Med Univ,2019,39(9):1065-1070.
［3］ 崔玉祥,李晨阳,朱丹,等.青藤碱通过调节Nrf2通路保护心肌细胞免受缺氧复氧损伤［J］.医学分子生物学杂志,2021,18(6):415-421. CUI YX,LI CY,ZHU D,et al.Sinsinine protects cardiomyocytes from hypoxic reoxygenation injury by regulating Nrf2 pathway ［J］.J Med Mol Biol,2021,18(6):415-421.
［4］ YU J,WANG S,CHEN SJ,et al.Sinomenine ameliorates fibroblast-like synoviocytes dysfunction by promoting phosphorylation and nuclear translocation of CRMP2［J］.J Ethnopharmacol,2024,2(1):117704.
［5］ 王新荣,张印坡,张延新.青藤碱抑制人卵巢癌SKOV3细胞活力、迁移和侵袭［J］.中国病理生理杂志,2018,34(5):793-798. WANG XR,ZHANG YP,ZHANG YX.Sinomenine inhibits SKOV3 cell viability,migration and invasion in human ovarian cancer ［J］.Chinese Journal of Pathophysiology,2018,34(5):793-798.
［6］ GUO J,TONG CY,SHI JG,et al.C-X-C motif chemokine ligand 12(CXCL12)/C-X-C motif chemokine receptor 7(CXCR7) regulates epithelial-mesenchymal transition process and promotes the metastasis of esophageal cancer by activating signal transducer and activator of transcription 3 (STAT3) pathway［J］.Bioengineered,2022,13(3):7425-7438.
［7］ XIE T,REN HY,LIN HQ,et al.Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway［J］.Int J Oncol,2016,48(5):2098-2112.
［8］ YUAN M,ZHAO B,JIA H,et al.Sinomenine ameliorates cardiac hypertrophy by activating Nrf2/ARE signaling pathway［J］.Bioengineered,2021,12(2):12778-12788.
［9］ 田颖颖,马贝贝,赵新月,等.青藤碱对人肝癌HepG2和SK-HEP-1细胞的抑制作用及分子机制研究［J］.中国中药杂志,2023,48(17):4702-4710. TIAN YY,MA BB,ZHAO XY,et al.Inhibitory effect of Sinomenine on human hepatocellular carcinoma HepG2 and SK-HEP-1 cells and its molecular mechanism ［J］.China Journal of Chinese Materia Medica,2023,48(17):4702-4710.
［10］ 吕彦霖,邓亚竹,朱昌毫,等.青藤碱对胆管癌细胞的抑制作用［J］.中成药,2022,44(6):1791-1798. LYU YL,DENG YZ,ZHU CH,et al.Inhibitory effect of sinsinine on bile duct cancer cells ［J］.Chinese Traditional Patent Medicine,2022,44(6):1791-1798.
［11］ 魏房,李震,周勇.青藤碱对肠癌细胞的抑制作用［J］.现代肿瘤医学，2019,27(05):750-753. WEI F,LI Z,ZHOU Y.Inhibitory effect of sinomenine on colon cancer cells［J］.Modern Oncology,2019,27(05):750-753.
［12］ 姜廷枢,李航,翟声平,等.青藤碱通过线粒体途径诱导肺癌NCI-H460细胞凋亡的初步研究［J］.现代肿瘤医学，2016,24(05):703-706. JIANG TS,LI H,ZHAI SP,et al.The primary research on sinomenine induced apoptosis of lung cancer NCI-H460 cells by the mitochondrial signaling pathway［J］.Modern Oncology,2016,24(05):703-706.
［13］ SONG L,ZHANG H,HU M,et al.Sinomenine inhibits hypoxia induced breast cancer side population cells metastasis by PI3K/Akt/mTOR pathway［J］.Bioorg Med Chem,2021,31(1):1-6.
［14］ QU X,YUB,ZHU M,et al.Sinomenine inhibits the growth of ovarian cancer cells through the suppression of mitosis by down-regulating the expression and the activity of CDK1［J］.Onco Targets Ther,2021,14(1):823-834.
［15］ QIN LN,ZHANG H,LI QQ,et al.Vitamin D binding protein (VDBP) hijacks twist1 to inhibit vasculogenic mimicry in hepatocellular carcinoma［J］.Theranostics,2024,14(1):436-450.
［16］ DAI T,LIU Y,CAO R,et al.CBX7 regulates metastasis of basal-like breast cancer through Twist1/EphA2 pathway［J］.Transl Oncol,2022,24(1):1-12.
［17］ 葛钰,卢林明,田澍雨,等.皖南蝮蛇毒抑瘤组分-Ⅰ通过MMP2抑制三阴性乳腺癌细胞体外血管生成拟态［J］.南方医科大学学报,2022,42(3):438-442. GE Y,LU LM,TIAN SY,et al.Antitumor component Ⅰ of Agkistrodon Agkistrodon venom inhibits in vitro angiogenesis mimicry of triple-negative breast cancer cells by MMP2［J］.J South Med Univ,2022,42(3):438-442.
［18］ LIU X,HE H,ZHANG F,et al.m6A methylated EphA2 and VEGFA through IGF2BP2/3 regulation promotes vasculogenic mimicry in colorectal cancer via PI3K/AKT and ERK1/2 signaling［J］.Cell Death Dis,2022,13(5):483-495.
［19］ FENG ZT,YANG T,HOU XQ,et al.Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis［J］.Biomed Pharmacother,2019,113(1):1-7.
［20］ SUN R,SUN Y,WU C,et al.CXCR4-modified CAR-T cells suppresses MDSCs recruitment via STAT3/NF-κB/SDF-1α axis to enhance efficacy against pancreatic cancer［J］.Mol Ther,2023,31(11):3193-3209.
［21］ CHO SJ,JEONG BY,SONG YS,et al.STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade［J］.Arch Pharm Res,2022,45(7):460-474.
［22］ HAN JH,YOON JS,CHANG DY,et al.CXCR4-STAT3 axis plays a role in tumor cell infiltration in an orthotopic mouse glioblastoma model［J］.Mol Cells,2020,43(6):539-550.
［23］ YUE D,ZHANG D,SHI X,et al.Chloroquine inhibits stemness of esophageal squamous cell carcinoma cells through targeting CXCR4-STAT3 pathway［J］.Front Oncol,2020,10(1):311-320.

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河南省医学科技攻关联合共建项目(编号：LHGJ2019010435)
Last Update: 1900-01-01