硫酸吲哚酯通过激活 AhR 和 Akt 促进结直肠癌细胞增殖和表皮生长因子受体表达增加。

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Yu Ichisaka, Shozo Yano, Kohji Nishimura, Toshimitsu Niwa, Hidehisa Shimizu
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引用次数: 0

摘要

虽然慢性肾脏病(CKD)患者罹患结直肠癌(CRC)的风险较高,但这两种疾病之间的联系并不十分清楚。最近的研究表明,CKD 和 CRC 的恶化都与肠道中产生吲哚的核酸镰刀菌数量增加密切相关。从肠道吸收的吲哚最终会在肝脏中代谢为硫酸吲哚酯。由于吲哚硫酸酯不仅参与加速慢性肾脏病的进展,还参与其相关并发症的发生和发展,因此本研究旨在明确吲哚硫酸酯是否会诱导 CRC 细胞增殖。本研究发现,硫酸吲哚酯通过激活芳基烃受体(AhR)和原癌基因Akt诱导来源于CRC的HCT-116细胞增殖。AhR拮抗剂CH223191和Akt抑制剂MK2206抑制了硫酸吲哚酯诱导的HCT-116细胞增殖。我们还发现,硫酸吲哚乙酯上调表皮生长因子受体(EGFR)的表达,这与 CRC 的不良预后有关,而 CH223191 和 MK2206 则抑制 EGFR 的表达。此外,吲哚硫酸酯通过上调表皮生长因子受体的表达,增加了 CRC 细胞对表皮生长因子的敏感性。这些研究结果表明,硫酸吲哚酯可能是慢性肾功能衰竭与 CRC 病情恶化之间的重要联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt.

Although patients with chronic kidney disease (CKD) have a higher risk of colorectal cancer (CRC) aggravation, the connection between these two diseases is not well understood. Recent studies have shown that both CKD and CRC aggravation are closely related to an increased abundance of indole-producing Fusobacterium nucleatum in the gut. The indole absorbed from the gut is eventually metabolized to indoxyl sulfate in the liver. Since indoxyl sulfate is involved not only in accelerating CKD progression but also in the initiation and development of its associated complications, the present study aimed to clarify whether indoxyl sulfate induces the proliferation of CRC cells. This study found that indoxyl sulfate induced the proliferation of CRC-derived HCT-116 cells by activating the aryl hydrocarbon receptor (AhR) and the proto-oncogene Akt. The AhR antagonist CH223191 and Akt inhibitor MK2206 suppressed indoxyl sulfate-induced proliferation of HCT-116 cells. We also found that indoxyl sulfate upregulated epidermal growth factor receptor (EGFR) expression, which is associated with poor prognosis of CRC, whereas CH223191 and MK2206 repressed EGFR expression. Furthermore, indoxyl sulfate increased the sensitivity of CRC cells to EGF by upregulating EGFR expression. These findings suggest that indoxyl sulfate may be an important link between CKD and CRC aggravation.

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来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
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