摘要
目的 探讨异紫堇碱(ICD)通过调控NDRG1/PI3K/AKT轴抑制卵巢癌生长与转移的机制。方法 采用不同浓度ICD干预卵巢癌细胞系OVCAR3,测定细胞增殖活力、凋亡与迁移情况;对裸鼠皮下注射OVCAR3细胞,成瘤后腹腔注射不同浓度ICD,观察瘤体生长情况。测定裸鼠肿瘤组织和OVCAR3细胞中NDRG1/PI3K/AKT轴蛋白表达情况;过表达NDRG1或敲降NDRG1后再次使用ICD干预OVCAR3细胞,并检测表型变化。结果 随着ICD干预剂量的增加,OVCAR3细胞体外增殖活力与迁移能力降低,细胞凋亡率升高,而裸鼠体内移植瘤生长减缓(P<0.05)。裸鼠肿瘤组织与OVCAR3细胞中NDRG1表达量亦随着ICD干预剂量的增加而升高(P<0.05),PI3K与AKT磷酸化水平随之降低(P<0.05)。过表达NDRG1同样抑制了OVCAR3细胞的增殖与转移,并促进了细胞凋亡(P<0.05);而沉默NDRG1则逆转了ICD抑制OVCAR3细胞恶性行为的效果(P<0.05)。结论 ICD通过上调NDRG1抑制了PI3K/AKT的活化,从而抑制了卵巢癌细胞的生长与转移。
Objective To investigate the mechanism of isocorydine(ICD) inhibiting the growth and metastasis of ovarian cancer by regulating NDRG1/PI3 K/AKT axis.Methods Ovarian cancer cell line OVCAR3 was intervened with different concentrations of ICD,and cell proliferation activity,apoptosis and cell migration ability were measured;then OVCAR3 cells were injected subcutaneously into nude mice,ICD were injected intraperitoneally after tumor formation and the growth of tumor was observed.The protein expression of NDRG1/PI3 K/AKT axis in tumor tissues of nude mice and OVCAR3 cells were measured;OVCAR3 cells with overexpression or silence of NDRG1 were treated with ICD,and their phenotypes were observed.Results Along with the increase of ICD intervention dose,the proliferation activity and migration ability of OVCAR3 cells in vitro decreased,the apoptosis rate increased,and the growth of transplanted tumors slowed down in nude mice(P<0.05).The expression of NDRG1 in tumor tissues of nude mice and OVCAR3 cells also increased with the increase of ICD intervention dose,and the phosphorylation levels of PI3 K and AKT decreased(P<0.05).Overexpression of NDRG1 also inhibited the proliferation and metastasis of OVCAR3 cells and promoted apoptosis(P<0.05),while silencing NDRG1 reversed the effect of ICD on the malignant behavior of OVCAR3 cells(P<0.05).Conclusions ICD inhibits the activation of PI3 K/AKT axis by up-regulating NDRG1,and thereby inhibiting the growth and metastasis of ovarian cancer cells.
作者
伦桂欢
覃筱婕
明子
李仲均
LUN Guihuan;QIN Xiaojie;MING Zi;LI Zhongjun(Department of Obstetrics and Gynecology,Dongguan People′s Hospital,Dongguan 523000,Guangdong,China)
出处
《中国性科学》
2022年第9期69-73,共5页
Chinese Journal of Human Sexuality
基金
广东省医学科学技术研究基金项目(C2017034)。
关键词
异紫堇碱
卵巢癌
转移
凋亡
Isocorydine
Ovarian cancer
Metastasis
Apoptosis
