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CICC 6074 菌 S 层蛋白对结肠癌 HT-29 细胞增殖和凋亡的影响。

Effect of CICC 6074 S-Layer Protein on Colon Cancer HT-29 Cell Proliferation and Apoptosis.

机构信息

Department of Food Science and Technology, School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, P. R. China.

College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, P. R. China.

出版信息

J Agric Food Chem. 2020 Mar 4;68(9):2639-2647. doi: 10.1021/acs.jafc.9b06909. Epub 2020 Feb 17.

Abstract

The objective of this research was to investigate the effects of CICC 6074 S-layer protein on the viability, adhesion, cell cycle, and apoptosis of human colon cancer HT-29 cells and to explore their molecular mechanism of tumor suppression. The S-layer protein at doses of 0, 25, 50, and 100 mg/L significantly suppressed the proliferation of HT-29 cells. The S-layer protein exerts its cytotoxic activities against colon cancer HT-29 cells by arresting the cell cycle in the G1 phase through upregulating the expression of p53, p21, and p16 and downregulating the expression of CDK1 (cyclin-dependent kinases) and cyclin B. Morphological changes were further observed by transmission electron microscopy, and the cells treated with the S-layer protein showed obvious characteristic changes of apoptosis including chromatin condensation, nuclear fragmentation, vacuoles, and so on. Furthermore, our mechanism studies indicated that the S-layer protein may induce HT-29 cell apoptosis through the death receptor apoptotic pathway and mitochondrial pathway and impede cell invasion by inhibiting the synthesis of the PI3K/AKT pathway and FasL. These results demonstrated that the CICC 6074 S-layer protein may be a potential anticarcinogenic agent.

摘要

本研究旨在探讨 CICC 6074 菌 S 层蛋白对人结肠癌 HT-29 细胞活力、黏附、细胞周期和凋亡的影响,并探讨其抑制肿瘤的分子机制。S 层蛋白在 0、25、50 和 100mg/L 剂量下显著抑制 HT-29 细胞的增殖。S 层蛋白通过上调 p53、p21 和 p16 的表达,下调 CDK1(细胞周期蛋白依赖性激酶)和细胞周期蛋白 B 的表达,将细胞周期阻滞在 G1 期,从而发挥对结肠癌 HT-29 细胞的细胞毒性作用。透射电镜进一步观察到形态学变化,用 S 层蛋白处理的细胞显示出凋亡的明显特征性变化,包括染色质浓缩、核碎裂、空泡等。此外,我们的机制研究表明,S 层蛋白可能通过死亡受体凋亡途径和线粒体途径诱导 HT-29 细胞凋亡,并通过抑制 PI3K/AKT 途径和 FasL 的合成来阻碍细胞侵袭。这些结果表明 CICC 6074 菌 S 层蛋白可能是一种有潜力的抗癌剂。

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