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青蒿素抑制葡萄糖刺激下结直肠癌细胞恶性生物学行为的机制研究

Mechanism of artemisinin inhibiting malignant biological behavior of colorectal cancer cells stimulated by glucose
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摘要 目的探讨青蒿素(ART)对葡萄糖刺激下结直肠癌(CRC)细胞的恶性生物学行为的影响及其作用机制。方法以0、5、10、20、40、60μmol/L ART为浓度梯度处理人结直肠癌细胞株SW480,然后采用CCK-8法检测细胞活力。流式细胞术检测细胞凋亡情况;Transwell检测细胞迁移和侵袭情况;Western blot检测细胞凋亡、上皮-间质转化(EMT)及Janus激酶2(JAK2)/信号转导与转录激活因子3(STAT3)相关蛋白表达。结果与0μmol/L ART相比,5、10、20、40、60μmol/L ART处理下SW480细胞活力降低(P<0.05),IC_(50)为36.91μmol/L。故以10、20、40μmol/L ART处理的细胞为ART低、中、高剂量组,以0μmol/L ART处理的细胞为对照组,以ART 40μmol/L+Coumermycin A110μmol/L处理的细胞为Coumermycin A1组。与对照组相比,ART低剂量组、ART中剂量组、ART高剂量组细胞划痕愈合率、侵袭能力及Bcl-2、N-cadherin、Vimentin、p-JAK2、p-STAT3表达显著下降(P<0.05),细胞凋亡率及Bax、Caspase-3、E-cadherin表达上升(P<0.05);与ART高剂量组相比,Coumermycin A1组细胞划痕愈合率、侵袭能力及Bcl-2、N-cadherin、Vimentin、p-JAK2、p-STAT3表达水平显著上升(P<0.05),细胞凋亡率及Bax、Caspase-3、E-cadherin表达水平下降(P<0.05)。结论ART可能通过抑制JAK2/STAT3信号通路,抑制葡萄糖刺激下CRC细胞活力、迁移、侵袭和EMT,促进其凋亡。 Objective To investigate the effect of artemisinin(ART)on the malignant biological behavior of colorectal cancer(CRC)cells stimulated by glucose and its mechanism.Methods The concentration gradients of 0,5,10,20,40 and 60µmol/L of ART were used to treat the human colorectal cancer cell line SW480,and then the cell viability was detected by CCK-8.Cell apoptosis was detected by flow cytometry.Transwell was used to detect the cell migration and invasion.Western blot was used to detect the apoptosis,epithelial-mesenchymal transition(EMT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)related proteins expression.Results Compared with the 0µmol/L of ART,the viability of SW480 cells decreased under 5,10,20,40,60µmol/L of ART treatment(P<0.05),and IC_(50) was 36.91µmol/L.Therefore,the cells treated with 10,20 and 40µmol/L of ART were as the low-dose,medium-dose and high-dose ART groups,the cells treated with 0µmol/L of ART were as the control group,and the cells treated with 40µmol/L of ART and 10µmol/L of Coumermycin A1 were as the Coumermycin A1 group.Compared with the control group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the low-dose ART group,the medium-dose ART group,and the high-dose ART group decreased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin increased(P<0.05).Compared with the high-dose ART group,the cell scratch wound healing rate,invasion ability,and expression levels of Bcl-2,N-cadherin,Vimentin,p-JAK2,and p-STAT3 in the Coumermycin A1 group increased obviously(P<0.05),while the apoptosis rate,and expression levels of Bax,Caspase-3 and E-cadherin decreased(P<0.05).Conclusion ART may inhibit the viability,migration,invasion and EMT of glucose-stimulated CRC cells and promote apoptosis by inhibiting the JAK2/STAT3 signaling pathway.
作者 潘勇娜 常月锋 郭璟静 孙依礼 魏岚 杨春雁 康金旺 PAN Yong-na;CHANG Yue-feng;GUO Jing-jing;SUN Yi-li;WEI Lan;YANG Chun-yan;KANG Jin-wang(Department of Gastroenterology,Second Affiliated Hospital of Hebei North University,Zhangjiakou Hebei 075100,China;School of Basic Medicine,Hebei North University,Zhangjiakou Hebei 075000,China)
出处 《局解手术学杂志》 2024年第5期388-393,共6页 Journal of Regional Anatomy and Operative Surgery
基金 河北省卫生健康委项目资助(20210473)。
关键词 青蒿素 结直肠癌 恶性生物学行为 Janus激酶2/信号转导与转录激活因子3 artemisinin colorectal cancer malignant biological behavior Janus kinase 2/signal transducer and activator of transcription 3
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