A novel antitumor mechanism of triptonide in colorectal cancer: inducing ferroptosis via the SLC7A11/GPX4 axis

IF 3.9 4区生物学 Q1 GENETICS & HEREDITY

Functional & Integrative Genomics Pub Date : 2024-07-16 DOI:10.1007/s10142-024-01402-2

Weijie Wang, Xiaofen Zhao, Jie Zhou, Hai Li

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Abstract

Colorectal cancer (CRC) is a prevalent malignancy affecting the human digestive tract. Triptonide has been shown to have some anticancer activity, but its effect in CRC is vague. Herein, we examined the effect of triptonide on CRC. In this study, the results of bioinformatics analysis displayed that triptonide may regulate ferroptosis in CRC by modulating GPX4 and SLC7A11. In HCT116 and LoVo cells, the expression levels of GPX4 and SLC7A11 were significantly reduced after triptonide management versus the control group. Triptonide inhibited proliferation, but promoted ferroptosis in CRC cells. SLC7A11 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide inhibited activation of the PI3K/AKT/Nrf2 signaling in CRC cells. Activation of the PI3K/AKT signaling or Nrf2 upregulation overturned the effects of triptonide on proliferation and ferroptosis in CRC cells. Triptonide suppressed CRC cell growth in vivo by modulating SLC7A11 and GPX4. In conclusion, Triptonide repressed proliferation and facilitated ferroptosis of CRC cells by repressing the SLC7A11/GPX4 axis through inactivation of the PI3K/AKT/Nrf2 signaling.

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三肽在结直肠癌中的新型抗肿瘤机制：通过 SLC7A11/GPX4 轴诱导铁变态反应

大肠癌（CRC）是影响人类消化道的一种常见恶性肿瘤。三苯氧胺已被证明具有一定的抗癌活性，但其对 CRC 的影响尚不明确。在此，我们研究了曲普奈德对 CRC 的影响。本研究的生物信息学分析结果显示，三肽可能通过调节 GPX4 和 SLC7A11 来调控 CRC 中的铁突变。与对照组相比，HCT116 和 LoVo 细胞中 GPX4 和 SLC7A11 的表达水平在三肽苷处理后显著降低。三苯氧胺抑制了 CRC 细胞的增殖，但促进了铁凋亡。SLC7A11 的上调推翻了三苯氧胺对 CRC 细胞增殖和铁突变的影响。曲普奈德抑制了 CRC 细胞中 PI3K/AKT/Nrf2 信号的激活。PI3K/AKT信号的激活或Nrf2的上调推翻了曲普奈德对CRC细胞增殖和铁突变的影响。曲普奈德通过调节 SLC7A11 和 GPX4 抑制了 CRC 细胞在体内的生长。总之，曲普奈德通过抑制SLC7A11/GPX4轴，使PI3K/AKT/Nrf2信号失活，从而抑制了CRC细胞的增殖并促进了铁氧化。

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来源期刊

Functional & Integrative Genomics 生物-遗传学

CiteScore

3.50

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?