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新分离的海洋细菌胞外多糖通过影响关键凋亡因子和激活 Toll 样受体增强 HepG2 细胞的抗肿瘤活性。

Newly isolated marine bacterial exopolysaccharides enhance antitumor activity in HepG2 cells via affecting key apoptotic factors and activating toll like receptors.

机构信息

Department of Hormones, Medical Research Division, National Research Centre, Dokki, Giza, P.O. 12622, Egypt.

Microbial Biotechnology Department, Genetic Engineering and Biotechnology Division, National Research Centre, Dokki, Giza, Egypt.

出版信息

Mol Biol Rep. 2019 Dec;46(6):6231-6241. doi: 10.1007/s11033-019-05061-6. Epub 2019 Sep 6.

Abstract

Hepatocellular carcinoma (HCC) was accompanied by high incidence of morbidity and mortality worldwide. Apoptosis is a vital biological process playing a critical role in cancer. Besides, toll like receptors were reported to regulator the innate immune response against cancer development. Exopolysaccharides (EPSs) derived from marine bacteria were reported to have a potential biological importance. This work aimed to elucidate the antitumor effects of newly isolated EPSs against HepG2 cells. Moreover, their effects on some apoptotic markers and TLRs were followed. Isolated EPSs were tested for their cytotoxic effects in a previous study and the most promising; MSA1, E4, MGA2, SGA3, and NRC7 EPSs were subjected to molecular analysis to investigate their pro-apoptotic effects, in addition to their effects on TLR2 and TLR-9 using quantitative real time RT-PCR. And the most cytotoxic and pro-apoptotic EPS; MSA1 were subjected to antibody array analysis to investigate a panel of 43 apoptotic proteins. All isolated EPSs produced a positive role in regulating the apoptotic gene and increasing the TLRs expression in different manners. However, the most promising EPS was MSA1. It showed pro-apoptotic effects on gene and protein levels, besides its up-regulation of TLRs.

摘要

肝细胞癌 (HCC) 在全球范围内发病率和死亡率都很高。细胞凋亡是一种重要的生物学过程,在癌症中起着关键作用。此外,Toll 样受体被报道能调节对癌症发展的固有免疫反应。从海洋细菌中提取的胞外多糖 (EPS) 具有潜在的生物学重要性。本工作旨在阐明新分离的 EPS 对 HepG2 细胞的抗肿瘤作用。此外,还研究了它们对一些凋亡标志物和 TLRs 的影响。在之前的研究中,对分离得到的 EPS 进行了细胞毒性测试,其中最有前途的是 MSA1、E4、MGA2、SGA3 和 NRC7 EPS,对其进行了分子分析,以研究它们的促凋亡作用,此外,还通过实时定量 RT-PCR 研究了它们对 TLR2 和 TLR-9 的影响。最具细胞毒性和促凋亡的 EPS;MSA1 进行了抗体阵列分析,以研究一组 43 种凋亡蛋白。所有分离的 EPS 都以不同的方式对凋亡基因的调节和 TLRs 的表达产生积极作用。然而,最有前途的 EPS 是 MSA1。它在基因和蛋白质水平上都表现出促凋亡作用,同时还上调了 TLRs。

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