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大蒜衍生的有机硫化合物通过激活丝裂原活化蛋白激酶(MAPK)途径和调节荷SGC-7901肿瘤小鼠的细胞因子发挥抗肿瘤功效。

Garlic-derived organosulfur compound exerts antitumor efficacy via activation of MAPK pathway and modulation of cytokines in SGC-7901 tumor-bearing mice.

作者信息

Jiang Xiaoyan, Zhu Xiaosong, Huang Weizhen, Xu Hongya, Zhao Zhongxi, Li Siying, Li Shanzhong, Cai Jianhua, Cao Jimin

机构信息

School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China.

School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, P.R. China; Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, P.R. China; Jiangsu Shengshi Kangde Biotech Corporation, Lianyungang, Jiangsu 222006, P.R. China.

出版信息

Int Immunopharmacol. 2017 Jul;48:135-145. doi: 10.1016/j.intimp.2017.05.004. Epub 2017 May 11.

DOI:10.1016/j.intimp.2017.05.004
PMID:28501767
Abstract

Diallyl trisulfide (DATS), a natural agent derived from garlic, has been tested for its antigastric cancer activities in various preliminary studies. However, more systematic pharmacodymatic (PD) and mechanistic evaluations are clearly needed. The aim of this study was to investigate the antitumor effects of DATS in the treatment of human gastric cancer cell SGC-7901 both in vitro and in vivo using widely recommended study procedures. DATS suppressed cancer cells proliferation and induced cell cycle arrest accompanied by an increase in the expressions of cyclin A2 and cyclin B1 in SGC-7901 cancer cells. DATS also caused an increase in apoptotic cell death, which involved in accumulations of bax, p53, and cytochrome C and reduction of Bcl-2 expressions. Besides, activation of JNK, ERK and p38 phosphorylation in DATS-treated cells suggested that mitogen-activated protein kinase (MAPKs) pathways were involved in DATS-induced apoptosis. Meanwhile, DATS significantly inhibited tumor growth and promoted tumor apoptosis in a xenograft model of gastric cancer cell SGC-7901. DATS inhibited tumor migration and invasion by modulating MMP9 and E-cadherin protein expressions. In addition, DATS treatment evidently increased the cytokine secretions of IL-12, TNF-α and IFN-γ (p<0.05). Biochemical serum analysis and histopathological examination indicated no obvious side effects in major mouse organs. Therefore, our findings provide a framework for further exploration of DATS as a novel chemotherapeutic for human gastric cancer.

摘要

二烯丙基三硫化物(DATS)是一种源自大蒜的天然物质,在各种初步研究中已对其抗胃癌活性进行了测试。然而,显然需要更系统的药效动力学(PD)和机制评估。本研究的目的是使用广泛推荐的研究程序,在体外和体内研究DATS对人胃癌细胞SGC - 7901的抗肿瘤作用。DATS抑制癌细胞增殖并诱导细胞周期停滞,同时SGC - 7901癌细胞中细胞周期蛋白A2和细胞周期蛋白B1的表达增加。DATS还导致凋亡细胞死亡增加,这涉及bax、p53和细胞色素C的积累以及Bcl - 2表达的降低。此外,DATS处理的细胞中JNK、ERK和p38磷酸化的激活表明丝裂原活化蛋白激酶(MAPKs)途径参与了DATS诱导的凋亡。同时,在胃癌细胞SGC - 7901的异种移植模型中,DATS显著抑制肿瘤生长并促进肿瘤凋亡。DATS通过调节MMP9和E - 钙黏蛋白的蛋白表达来抑制肿瘤迁移和侵袭。此外,DATS处理明显增加了IL - 12、TNF - α和IFN - γ的细胞因子分泌(p<0.05)。生化血清分析和组织病理学检查表明,主要小鼠器官无明显副作用。因此,我们的研究结果为进一步探索DATS作为一种新型人类胃癌化疗药物提供了框架。

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