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γ-生育三烯酚通过靶向 Notch 信号通路调控胃癌。

γ-tocotrienol regulates gastric cancer by targeting notch signaling pathway.

机构信息

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.

College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.

出版信息

Hereditas. 2023 Apr 13;160(1):15. doi: 10.1186/s41065-023-00277-w.

DOI:10.1186/s41065-023-00277-w
PMID:37055846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10100483/
Abstract

BACKGROUND

Gastric cancer is a common cause of death from cancer and an important global health care issue. Consequently, there is an urgent need to find new drugs and therapeutic targets for the treatment of gastric cancer. Recent studies have shown that tocotrienols (T3) have significant anticancer ability in cancer cell lines. Our previous study found that γ-tocotrienol (γ-T3) induced apoptosis in gastric cancer cells. We further explored the possible mechanisms of γ-T3 therapy for gastric cancer.

METHODS

In this study, we treated gastric cancer cells with γ-T3, collect and deposit the cells. γ-T3-treated gastric cancer cells group and untreated group were subjected to RNA-seq assay, and analysis of sequencing results.

RESULTS

Consistent with our previous findings, the results suggest that γ-T3 can inhibit mitochondrial complexes and oxidative phosphorylation. Analysis reveals that γ-T3 has altered mRNA and ncRNA in gastric cancer cells. Significantly altered signaling pathways after γ-T3 treatment were enriched for human papillomavirus infection (HPV) pathway and notch signaling pathway. The same significantly down-regulated genes notch1 and notch2 were present in both pathways in γ-T3-treated gastric cancer cells compared to controls.

CONCLUSIONS

It is indicated that γ-T3 may cure gastric cancer by inhibiting the notch signaling pathway. To provide a new and powerful basis for the clinical treatment of gastric cancer.

摘要

背景

胃癌是癌症死亡的常见原因,也是一个重要的全球医疗保健问题。因此,迫切需要寻找治疗胃癌的新药和治疗靶点。最近的研究表明,生育三烯酚(T3)在癌细胞系中具有显著的抗癌能力。我们之前的研究发现,γ-生育三烯酚(γ-T3)可诱导胃癌细胞凋亡。我们进一步探讨了 γ-T3 治疗胃癌的可能机制。

方法

在这项研究中,我们用 γ-T3 处理胃癌细胞,收集和储存细胞。γ-T3 处理的胃癌细胞组和未处理组进行 RNA-seq 分析,并对测序结果进行分析。

结果

与我们之前的发现一致,结果表明 γ-T3 可以抑制线粒体复合物和氧化磷酸化。分析显示,γ-T3 改变了胃癌细胞中的 mRNA 和 ncRNA。经 γ-T3 处理后,信号通路发生显著改变,人乳头瘤病毒(HPV)感染途径和 Notch 信号通路富集。与对照组相比,在 γ-T3 处理的胃癌细胞中,两条通路中均存在 Notch1 和 Notch2 这两个显著下调的基因。

结论

表明 γ-T3 可能通过抑制 Notch 信号通路来治愈胃癌。为胃癌的临床治疗提供了新的有力依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/831eec835790/41065_2023_277_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/b5606fe78767/41065_2023_277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/e0f85fc954f8/41065_2023_277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/6a6e4663c2d5/41065_2023_277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/150aaac03c03/41065_2023_277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/1e25be408092/41065_2023_277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/b555e469b0ba/41065_2023_277_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/831eec835790/41065_2023_277_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/b5606fe78767/41065_2023_277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/e0f85fc954f8/41065_2023_277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/6a6e4663c2d5/41065_2023_277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/150aaac03c03/41065_2023_277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/1e25be408092/41065_2023_277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/b555e469b0ba/41065_2023_277_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec9e/10100483/831eec835790/41065_2023_277_Fig7_HTML.jpg

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