草果诱导卵巢癌细胞凋亡的机制研究  

Study on mechanism of apoptosis in ovarian cancer cells induced by Amomum tsao-ko under endoplasmic reticulum stress

作　　者：李书帆 江汉美[1] 韩蔓 田宇 刘天琪 刘毅[1] LI Shufan;JIANG Hanmei;HAN Man;TIAN Yu;LIU Tianqi;LIU Yi(Hubei Research and Development Center for Medicinal Plants,Hubei University of Traditional Chinese Medicine,Wuhan,Hubei,430065 P.R.China)

机构地区：[1]湖北中医药大学湖北省药用植物研发中心,湖北武汉430065

出　　处：《华西药学杂志》2023年第1期37-42,共6页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:81772491)。

摘　　要：目的 评估草果杀伤卵巢癌细胞的能力并阐明其作用机制。方法 通过流式细胞术、Western blot法、ELISA法、GEPIA2.0数据库、体内动物实验等,评估内质网应激、白细胞介素-6(IL-6)和叉头框蛋白(FOXO3a)在草果乙醇提取物(ATEE)诱导卵巢癌细胞SKOV3凋亡过程中的作用及相互调节关系。结果 在细胞水平,浓度大于20μg·mL^(-1)的ATEE均显著增加SKOV3细胞的凋亡率,呈现浓度依赖性。ATEE能够上调SKOV3细胞中GRP78、CHOP、FOXO3a蛋白的表达水平,并显著抑制IL-6的分泌。沉默SKOV3细胞CHOP基因、FOXO3a基因或加入外源IL-6,均能逆转ATEE诱导SKOV3细胞凋亡的能力。进一步证实,沉默SKOV3细胞CHOP基因,能够逆转ATEE上调FOXO3a蛋白水平的能力和抑制IL-6分泌的能力。TCGA数据库分析结果表明:在mRNA水平上,FOXO3a与内质网应激激活正相关。在动物水平,ATEE显著抑制荷瘤小鼠的瘤重。结论 ATEE可能是通过激活SKOV3细胞内质网应激来抑制IL-6的分泌,并上调FOXO3a蛋白,从而诱导SKOV3细胞凋亡。OBJECTIVE To confirm the inhibition ability of Amomum tsao-ko on ovarian cancer cells, and to elucidate its mechanism.METHODS Flow cytometry, Western blot, enzyme-linked immunosorbent assay(ELISA),GEPIA2.0 database and in vivo animal experiments were performed to evaluate the role of endoplasmic reticulum stress, IL-6 and FOXO3a in the apoptosis of ovarian cancer cells(SKOV3) induced by ethanol extract of Amomum Tsao-ko(ATEE).RESULTS At the cellular level, ATEE at concentrations above 20 μg·mL^(-1)significantly increased the apoptosis rate of SKOV3 cells in a concentration-dependent manner.ATEE up-regulated the protein expression levels of GRP78,CHOP and FOXO3a in SKOV3 cells, and significantly inhibited the secretion of IL-6 in SKOV3 cells.Silencing CHOP gene, FOXO3a gene or adding exogenous IL-6 could reverse the ability of ATEE to induce apoptosis of SKOV3 cells.It was further confirmed that silencing CHOP gene in SKOV3 cells could reverse the ability of ATEE to up-regulate FOXO3a protein level and inhibit IL-6 secretion.TCGA database analysis showed that FOXO3a was positively correlated with ER stress activation at mRNA level.At the animal level, ATEE significantly inhibited tumor weight in tumor-bearing mice.CONCLUSION ATEE activates ER stress to inhibit the secretion of IL-6 in ovarian cancer cells, and induces the up-regulation of FOXO3a, which leads to the apoptosis on SKOV3 cells.

关 键 词：草果 乙醇提取物 卵巢癌细胞 内质网应激 白细胞介素-6 叉头框蛋白 GRP78 CHOP GEPIA2.0数据库 

分 类 号：R96[医药卫生—药理学]