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| Impacts of Oleuropein on the Malignant Biological Behavior of Cholangiocarcinoma Cells by Regulating the JAK2/STAT3 Signaling Pathway |
| ZHENG Wei, HAN Chao |
| Shaanxi Nuclear Industry 215 Hospital, Shaanxi Xianyang 712000, China |
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Abstract Objective: To investigate the impacts of Oleuropein (Ole) on the malignant biological behavior of cholangiocarcinoma cells by regulating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.Methods: HuCCT1 cells in logarithmic growth phase were divided into control group, 100μg/mL Ole group, 200μg/mL Ole group, 400μg/mL Ole group, 800μg/mL Ole group, and Ole+JAK2/STAT3 signaling pathway activator (Colivelin) group. The control group was not treated, and HuCCT1 cells in 100μg/mL Ole group, 200μg/mL Ole group, 400μg/mL Ole group, and 800μg/mL Ole groups were treated with 100, 200, 400, and 800μg/mL Ole, and the Ole+Colivelin group treated HuCCT1 cells with (800μg/mL Ole and 0.5μmoL/L Colivelin respectively). CCK-8 method, plate cloning method, and flow cytometry were applied to determine cell viability, cloning, and apoptosis, respectively. Transwell experiment was applied to detect cell migration and invasion. Western blot was applied to determine the expression of JAK2/STAT3 signaling pathway proteins and apoptotic proteins.Results: The HuCCT1 cell viability and number of cloned cells in the 100, 200, 400, and 800μg/mL Ole groups were lower than those in the control group, and the apoptosis rate was higher than that in the control group, the trend of change was Ole dose-dependent (P<0.05). Compared with the 800μg/mL Ole group, the HuCCT1 cell viability and number of cloned cells in the Ole+Colivelin group increased, while the apoptosis rate decreased (P<0.05). Compared with the control group, the migration and invasion of HuCCT1 cells in the 100, 200, 400, and 800μg/mL Ole groups showed an Ole dose-dependent decrease (P<0.05). Compared with the 800μg/mL Ole group, the migration and invasion of HuCCT1 cells in the Ole+Colivelin group increased (P<0.05). Compared with the control group, the protein expression of p-JAK2/JAK2, p-STAT3/STAT3, and Bcl-2 in HuCCT1 cells in the 100, 200, 400, and 800μg/mL Ole groups showed an Ole dose-dependent decrease, the protein expression of Bax showed an Ole dose-dependent increase (P<0.05). Compared with the 800μg/mL Ole group, the expression of p-JAK2/JAK2, p-STAT3/STAT3, and Bcl-2 proteins in HuCCT1 cells in the Ole+Colivelin group increased, the protein expression of Bax decreased (P<0.05). Conclusion:Ole may inhibit the malignant biological behavior of cholangiocarcinoma cells by inhibiting the activation of the JAK2/STAT3 signaling pathway.
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[1] Kidanemariam S,Gu J,Yoon JH,et al.Cholangiocarcinoma:epidemiology and imaging-based review[J].R I Med (2013),2024,107(5):43-48.
[2] Cheng H,Li Q.Sevoflurane inhibits cholangiocarcinoma via Wnt/β-catenin signaling pathway[J].BMC Gastroenterol,2023,23(1):279-287.
[3] Junkins K,Rodgers M,Phelan SA.Oleuropein induces cytotoxicity and peroxiredoxin over-expression in MCF-7 human breast cancer cells[J].Anticancer Res,2023,43(10):4333-4339.
[4] Rishmawi S,Haddad F,Dokmak G,et al.A comprehensive review on the anti-cancer effects of oleuropein[J].Life (Basel),2022,12(8):1140-1157.
[5] 文礼,李春姗,李娇,等.干扰NETO2通过调控JAK2/STAT3信号通路抑制肺腺癌细胞增殖和转移能力[J].国际检验医学杂志,2023,44(14):1762-1767.
[6] Jantalika T,Manochantr S,Kheolamai P,et al.Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines[J].Sci Rep,2022,12(1):11341.
[7] Lu HY,Zhu JS,Xie J,et al.Hydroxytyrosol and oleuropein inhibit migration and invasion via induction of autophagy in ER-positive breast cancer cell lines (MCF7 and T47D)[J].Nutr Cancer,2021,73(2):350-360.
[8] 杨春洁,李天柱.橄榄苦苷通过调控ELK-3抑制人肝癌细胞上皮-间质转化的机制研究[J].北京医学,2022,44(3):241-244.
[9] 朱丽,胡朝霞,胡瑞晴.苦参碱调控JAK2/STAT3通路影响肝癌细胞迁移、侵袭和EMT的作用研究[J].现代消化及介入诊疗,2023,28(8):976-980.
[10] Park KH,Joo SH,Seo JH,et al.Licochalcone H induces cell cycle arrest and apoptosis in human skin cancer cells by modulating JAK2/STAT3 signaling[J].Biomol Ther (Seoul),2022,30(1):72-79.
[11] 张伟,于鸣,李伟,等.白皮杉醇调节JAK2/STAT3信号通路对胆囊癌细胞恶性生物学行为的影响[J].河北医药,2023,45(14):2090-2094. |
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2024, Vol. 30 
