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黄芪甲苷调控JAK2/STAT3信号通路增强宫颈癌HeLa细胞对紫杉醇的化疗敏感性 被引量:4

Astragaloside IV Enhancing Chemosensitivity of Cervical Cancer Hela Cells to Paclitaxel by Regulating JAK2/STAT3 Signaling Pathway
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摘要 目的:研究黄芪甲苷对宫颈癌HeLa细胞紫杉醇化疗敏感性的增强作用及其机制。方法:实验选用宫颈癌HeLa细胞,采用不同浓度紫杉醇和黄芪甲苷处理后,MTT实验检测细胞存活率;流式细胞仪检测细胞周期变化及细胞凋亡情况;Hoechst 33342染色观察细胞核形态变化;细胞划痕实验检测细胞迁移率;Western Blot检测Janus激酶2(janus kinase 2,JAK2)/信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)信号通路相关蛋白表达水平。结果:与对照组比较,当黄芪甲苷浓度≥40 mg·L^(-1)及紫杉醇的浓度≥40μmol·L^(-1)时,HeLa细胞存活率明显降低(P<0.05)。与对照组比较,紫杉醇组细胞存活率、细胞周期、细胞凋亡、细胞迁移率及相关蛋白表达水平无明显变化(P>0.05);与紫杉醇组比较,紫杉醇+黄芪甲苷中、高剂量组细胞存活率、S期及G2/M期细胞占比、细胞迁移率和p-STAT3、p-JAK2、B细胞淋巴瘤基因-2(B-cell lymphoma-2,Bcl-2)蛋白表达水平显著降低(P<0.01);G0/G1期细胞占比、早期凋亡细胞比例及Bcl-2相关X蛋白(Bcl-2 assaciated X protein,Bax)、细胞周期蛋白D1(Cyclin D1)、细胞周期蛋白依赖性激酶4(cyclin dependent kinase 4,CDK4)蛋白表达水平显著升高(P<0.05)。激光共聚焦显微镜观察发现:对照组细胞核形态均一,而紫杉醇+黄芪甲苷中、高剂量组细胞出现明显凋亡特征,如细胞变形、核皱缩、染色质凝缩等。结论:黄芪甲苷可以增强宫颈癌HeLa细胞对紫杉醇的化疗敏感性,其机制可能与调控JAK2/STAT3信号通路相关。 Objective:To study the enhancement effect and mechanism of astragaloside IV on the chemosensitivity of cervical cancer HeLa cells to paclitaxel.Methods:Cervical cancer HeLa cells were selected in the experiment and treated with different concentrations of paclitaxel and astragaloside IV,and the cell viability was detected by MTT assay.Flow cytometry was used to detect cell cycle changes and apoptosis.Hoechst 33342 staining was used to observe the changes in nuclear morphology.Cell scratch experiments were used to detect cell migration rate.Western Blot was used to detect the expression levels of proteins related to the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Results:Compared with the control group,when the concentration of astragaloside IV≥40 mg·L^(-1) and the concentration of paclitaxel≥40μmol·L^(-1),the survival rate of HeLa cells was significantly decreased(P<0.05).Compared with the control group,the cell survival rate,cell cycle,cell apoptosis,cell migration rate and the expression levels of related proteins in the paclitaxel group had no significant changes(P>0.05).Compared with the paclitaxel group,the paclitaxel+astragaloside IV medium and high dose groups showed cell survival rate,S phase and G2/M phase cell proportions,cell migration rate and p-STAT3,p-JAK2,B-cell lymphoma-2(Bcl-2)protein expression level was significantly decreased(P<0.01).The proportion of cells in G0/G1 phase,the proportion of early apoptotic cells,Bcl-2 associated X protein(Bax),Cyclin D1,cyclin dependent kinase 4(CDK4)protein expression level was significantly increased(P<0.05).Laser confocal microscope observation showed that the nucleus of the control group was uniformly stained,while the cells in the paclitaxel+astragaloside IV medium and high dose groups had obvious apoptosis characteristics,such as cell deformation,nuclear shrinkage,and chromatin condensation.Conclusion:Astragaloside IV can enhance the chemosensitivity of cervical cancer HeLa cells to paclitaxel,and
作者 何瑞荣 胡润凯 韩伟超 邵颖颖 李灿涛 丁少波 HE Ruirong;HU Runkai;HAN Weichao;SHAO Yingying;LI Cantao;DING Shaobo(Dongguan People′s Hospital Affiliated to Southern Medical University,Dongguan Guangdong China 523059)
出处 《中医学报》 CAS 2022年第12期2649-2656,共8页 Acta Chinese Medicine
基金 广东省中医药局“十三五”中医重点特色专科建设项目(粤中医函〔2019〕472号) 东莞市社会发展科技重点项目(20211800905242)。
关键词 宫颈癌 紫杉醇 黄芪甲苷 JAK2/STAT3信号通路 化疗敏感性 cervical cancer paclitaxel astragaloside IV JAK2/STAT3 signaling pathway chemosensitivity
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