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丁香酸对结直肠癌的体外和体内抗癌作用:可能的机制观点。

In vitro and in vivo anticancer effects of syringic acid on colorectal cancer: Possible mechanistic view.

机构信息

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Chem Biol Interact. 2021 Mar 1;337:109337. doi: 10.1016/j.cbi.2020.109337. Epub 2021 Feb 4.

DOI:10.1016/j.cbi.2020.109337
PMID:33548266
Abstract

This study aimed to evaluate the in vitro effects of syringic acid on human colorectal cancer cells (SW-480) and the effect of orally administered syringic acid on in vivo models of colorectal cancer induced in rats by administration of 1,2-dimethylhydrazine (DMH). In vitro effects of syringic acid treatment on human colorectal cancer SW-480 cell lines were assessed by performing cell proliferation assay (MTT and Trypan Blue staining), apoptosis assays (TUNEL assay, Annexin-V/PI flowcytometry and lactate dehydrogenase release assay), measuring reactive oxygen species (ROS), antioxidant enzymes and DNA damage, and evaluating protein levels of proliferative genes, and autophagy markers. In vitro anti-cancer roles of syringic acid were studied in rats with DMH-induced colorectal cancer cells. The effect of orally administered syringic acid (50 mg/kg) on tumor growth and incidence was studied in four groups (n = 6) of animals injected with DMH and treated for 15 weeks. Syringic acid treatment resulted in a significant dose-dependent inhibition of cellular proliferation, induction of apoptosis through increasing cellular ROS and DNA damage levels, as well as downregulating major proliferative genes. In vivo, treatment of rats with syringic acid demonstrated a statistically significant tumor volume and incidence reduction when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered syringic acid on colorectal tumors in rats.

摘要

本研究旨在评估丁香酸对人结直肠癌细胞(SW-480)的体外作用,以及口服丁香酸对 1,2-二甲基肼(DMH)诱导大鼠结直肠癌细胞体内模型的影响。通过进行细胞增殖测定(MTT 和台盼蓝染色)、凋亡测定(TUNEL 测定、Annexin-V/PI 流式细胞术和乳酸脱氢酶释放测定)、测量活性氧(ROS)、抗氧化酶和 DNA 损伤,以及评估增殖基因和自噬标志物的蛋白水平,评估丁香酸处理对人结直肠癌细胞 SW-480 细胞系的体外作用。在 DMH 诱导的结直肠癌细胞大鼠中研究了丁香酸的体外抗癌作用。在注射 DMH 并治疗 15 周的四组(n = 6)动物中,研究了口服丁香酸(50mg/kg)对肿瘤生长和发生率的影响。丁香酸处理导致细胞增殖显著的剂量依赖性抑制,通过增加细胞 ROS 和 DNA 损伤水平,以及下调主要增殖基因,诱导细胞凋亡。体内,与对照组相比,用丁香酸治疗大鼠可显著降低肿瘤体积和发生率。这是首例证明口服丁香酸对大鼠结直肠肿瘤具有体内生长抑制作用的研究。

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