Zhang Xinrui, Wang Yingwu, Li Xin, Yang Anhui, Li Zhiwen, Wang Di
School of Life Sciences, Jilin University, Changchun 130012, China.
Zhuhai College of Jilin University, Jilin University, Zhuhai 519041, China.
Aging (Albany NY). 2019 Nov 20;11(22):10284-10300. doi: 10.18632/aging.102456.
In this study, erianin was found to reduce the viability of cancer cells, inhibit their proliferation and migration, induce G2/M phase arrest, enhance cancer cell apoptosis, promote an increase in levels of intracellular reactive oxygen species and a decrease in mitochondrial membrane potential, and regulate the expression levels of anti- and pro-apoptosis-related proteins in HepG2 and SMMC-7721 cells. Erianin inhibited tumor growth in HepG2- and SMMC-7721-xenograft tumor nude mouse models, reduced the expression levels of anti-apoptosis proteins and enhanced the expression levels of pro-apoptosis proteins in tumor tissues. Erianin inhibited tumor growth in immunosuppressed BALB/c mice bearing heterotopic tumors. Among 111 types of cytokines detected in proteome profiling of tumor tissues, erianin substantially influenced levels of 38 types of cytokines in HepG2-xenografted tumors and of 15 types of cytokines in SMMC-7721-xenografted tumors, most of which are related to immune functions. Erianin strongly affected the serum levels of cytokines, and regulated the activation of nuclear factor-kappa B (NF-κB), and the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins in spleen. The anti-liver cancer properties of erianin were found to be related mostly to its modulation of oxidative stress-mediated mitochondrial apoptosis and immune response.
在本研究中，发现毛兰素可降低癌细胞的活力，抑制其增殖和迁移，诱导G2/M期阻滞，增强癌细胞凋亡，促进细胞内活性氧水平升高和线粒体膜电位降低，并调节HepG2和SMMC-7721细胞中抗凋亡和促凋亡相关蛋白的表达水平。毛兰素在HepG2和SMMC-7721异种移植瘤裸鼠模型中抑制肿瘤生长，降低肿瘤组织中抗凋亡蛋白的表达水平并增强促凋亡蛋白的表达水平。毛兰素在荷异位肿瘤的免疫抑制BALB/c小鼠中抑制肿瘤生长。在肿瘤组织蛋白质组分析中检测的111种细胞因子中，毛兰素显著影响HepG2异种移植瘤中38种细胞因子的水平以及SMMC-7721异种移植瘤中15种细胞因子的水平，其中大多数与免疫功能相关。毛兰素强烈影响细胞因子的血清水平，并调节核因子-κB（NF-κB）的激活以及脾脏中核因子红细胞2相关因子2（Nrf2）及其下游蛋白的表达水平。发现毛兰素的抗肝癌特性主要与其对氧化应激介导的线粒体凋亡和免疫反应的调节有关。
