山竹醇介导JAK2/STAT3信号通路发挥抗骨肉瘤作用  

Anti-osteosarcoma Effect of Garcinol by Mediating JAK2/STAT3 Signaling Pathway

作　　者：宋奇 程安源 徐立[1] 余铃[2] 夏平[1] Song Qi;Cheng Anyuan;Xu Li(Department of Orthopedics,Wuhan First People′s Hospital,Hubei 430022,China)

机构地区：[1]武汉市第一医院骨科,430022 [2]武汉大学人民医院骨科,430060

出　　处：《医学研究杂志》2020年第9期36-41,共6页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81502575)。

摘　　要：目的探究山竹醇对骨肉瘤细胞活力、细胞周期分布和凋亡的影响及对裸鼠皮下骨肉瘤生长的影响并探究其作用机制。方法采用CCK-8实验检测山竹醇对骨肉瘤细胞活力的影响;流式细胞术分析山竹醇对骨肉瘤细胞凋亡率及细胞周期分布的影响;构建裸鼠皮下骨肉瘤模型,检测山竹醇腹腔注射对裸鼠皮下骨肉瘤生长的影响;RNA测序分析检测山竹醇处理骨肉瘤细胞后改变的基因;Western blot法检测山竹醇对骨肉瘤细胞及肿瘤组织中JAK2/STAT3信号通路的影响。结果CCK-8法检测结果表明,山竹醇能时间、浓度依耐性的抑制骨肉瘤U2OS细胞活力;流式细胞术检测结果表明,山竹醇能诱导U2OS细胞凋亡,并导致细胞周期阻滞于S期。并且,山竹醇能抑制裸鼠皮下骨肉瘤的生长。基因富集分析结果表明,山竹醇处理的骨肉瘤细胞中JAK/STAT信号通路显著富集。Western blot法检测结果表明,山竹醇处理骨肉瘤细胞及骨肉瘤组织中p-JAK2、p-STAT3、Bcl-xl水平明显降低,而Bax表达水平显著升高。结论山竹醇能可在体内体外发挥抗骨肉瘤作用,可能与其抑制骨肉瘤中JAK2/STAT3信号通路活性有关。Objective To study the effect of garcinol on cell viability,cell cycle distribution,apoptosis of osteosarcoma cells and the growth of subcutaneous tumor in nude mice and further explore its mechanism.Methods U2OS cells were treated with vary concentrations of garcinol.The cell viability of osteosarcoma cells were detected by CCK-8 assay.The cell cycle distribution and apoptosis rate of U2OS cells were determined by flow cytometry.The subcutaneous osteosarcoma model of nude mice was constructed to detect the effect of garcinol intraperitoneal injection on the growth of subcutaneous tumor of nude mice.RNA-Sequence analysis was used to detected genes influenced by garcinol treatment.The expression levels of proteins in JAK2/STAT3 signal pathway were detected by Western blot.Results CCK-8 assay showed that garcinol reduces cell viability of U2OS cells in a concentration-and time-dependent manner.The results of flow cytometry suggested that garcinol treatment could arrest cell cycle at S phase and induce apoptosis of osteosarcoma cells.Furthermore,garcinol inhibited the growth of subcutaneous tumor in nude mice.Gene-Set Enrichment Analysis showed that JAK/STAT signaling pathway was significant enriched in garcinol treated osteosarcoma cells.The expression levels of p-JAK2,p-STAT3,Bcl-xl were significantly decreased and the expression level of Bax were significantly increased in osteosarcoma cells and osteosarcoma tumor tissues treated with garcinol.Conclusion Garcinol exerts anti-osteosarcoma effect in vitro and in vivo,which may be related to the down-regulation of JAK2/STAT3 signaling pathway.

关 键 词：山竹醇 骨肉瘤 细胞活力 JAK2/STAT3信号通路 

分 类 号：R681[医药卫生—骨科学]