New Treatment Modalities for Colorectal Cancer Through Simultaneous Suppression of FSP1 and GPX4.

IF 1.6 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17316

Chiharu Yasui, Yusuke Kono, Ryo Ishiguro, Takuki Yagyu, Kihara Kyoichi, Manabu Yamamoto, Tomoyuki Matsunaga, Shuichi Takano, Naruo Tokuyasu, Teruhisa Sakamoto, Toshimichi Hasegawa, Yoshihisa Umekita, Yoshiyuki Fujiwara

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Abstract

Background/aim: Ferroptosis is a nonapoptotic type of cell death that is dependent on iron and involves the accumulation of reactive oxygen species. Ferroptosis suppressor protein 1 (FSP1) and glutathione peroxidase 4 (GPX4) are ferroptosis regulators that inhibit ferroptosis through independent pathways. This study assessed the prognostic value of GPX4 and FSP1 expression in colorectal cancer (CRC). We also examined the effects of FSP1 and GPX4 inhibition on cell survival of CRC cells.

Materials and methods: This study included 206 surgical specimens from Stage II or III CRC patients. FSP1 and GPX4 expression was analyzed immunohistochemically, and the association of their expression levels with clinical outcome was evaluated. We also examined the effects of FSP1 and GPX4 inhibitors on the cell proliferative capacity of CRC cell lines.

Results: Overall survival and recurrence-free survival were reduced in patients with high expression of FSP1 or GPX4, and those with both GPX4 and FSP1 expression showed worse prognosis. Positivity of both FSP1 and GPX4 was an independent poor prognostic factor for CRC patients. In CRC cells, the combination of GPX4 and FSP1 inhibitors led to more effective cell death than either inhibitor alone.

Conclusion: High expression of both GPX4 and FSP1 is a significant poor prognostic factor for CRC. Simultaneous inhibition of GPX4 and FSP1 to induce ferroptosis may be a novel therapeutic strategy in CRC.

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通过同时抑制 FSP1 和 GPX4 治疗结直肠癌的新方法

背景/目的：铁凋亡是一种非凋亡性细胞死亡，它依赖于铁并涉及活性氧的积累。铁凋亡抑制蛋白1（FSP1）和谷胱甘肽过氧化物酶4（GPX4）是铁凋亡调节因子，它们通过独立的途径抑制铁凋亡。本研究评估了 GPX4 和 FSP1 表达在结直肠癌（CRC）中的预后价值。我们还研究了抑制 FSP1 和 GPX4 对 CRC 细胞存活的影响：本研究纳入了 206 例 II 期或 III 期 CRC 患者的手术标本。对 FSP1 和 GPX4 的表达进行了免疫组化分析，并评估了它们的表达水平与临床结果的关系。我们还研究了FSP1和GPX4抑制剂对CRC细胞系细胞增殖能力的影响：结果：FSP1或GPX4高表达的患者总生存期和无复发生存期均缩短，GPX4和FSP1均表达的患者预后更差。FSP1和GPX4同时阳性是CRC患者预后不良的独立因素。在 CRC 细胞中，联合使用 GPX4 和 FSP1 抑制剂比单独使用其中一种抑制剂能更有效地导致细胞死亡：结论：GPX4 和 FSP1 的高表达是导致 CRC 预后不良的重要因素。同时抑制 GPX4 和 FSP1 以诱导铁变态反应可能是治疗 CRC 的一种新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.