Scholarlink

Background <p>Gastric cancer (GC), known for its aggressive growth and metastasis, remains a leading cause of cancer-related mortality. Although Timosaponin B-II (TB-II) from <i>Anemarrhena asphodeloides</i> has shown anticancer potential, its underlying mechanisms in GC are not yet fully understood.</p> Methods <p>Our study investigates and compares the expression patterns of Kruppel-Like Factor 6(KLF6) in GC tissues across different TNM stages, while exploring its upstream regulatory factors. GC cells were treated with Timosaponin B-II (TB-II), and alterations in cell proliferation and apoptosis rates were evaluated using CCK-8 and TUNEL assays. Furthermore, the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2), miR-455-3p, and KLF6 were quantified to elucidate the mechanisms underlying TB-II’s effects. To confirm the interaction between miR-455-3p and KLF6, as well as Nrf2 and miR-455-3p, bioinformatics analysis, luciferase assays, and ChIP-PCR were conducted. Finally, protein synthesis and degradation assays were performed to explore the mechanism by which TB-II regulates the expression and activity of Nrf2.</p> Results <p>Both mRNA and protein expression levels of KLF6 were significantly lower in GC tissues compared to adjacent normal tissues. Notably, only KLF6 protein expression exhibited a decline in GC tissues from stages I to III of GC, whereas its upstream regulator, miR-455-3p, displayed the opposite trend. Treatment with TB-II markedly inhibited GC cells proliferation and induced apoptosis in a dose-dependent manner. Mechanistically, TB-II treatment upregulated the expression of Kelch-like ECH-associated protein 1(Keap1) protein, facilitating the formation of the Keap1/Nrf2 complex, which enhanced the ubiquitin-mediated degradation of Nrf2 in GC cells. Consequently, the transcriptional activation of miR-455-3p by Nrf2 was suppressed, resulting in the upregulation of the tumor suppressor KLF6. Silencing KLF6 can counteract the effects of TB-II in inhibiting proliferation and promoting apoptosis in GC cells.</p> Conclusion <p>TB-II suppresses GC cell proliferation and induces apoptosis via the Nrf2/miR-455-3p/KLF6 pathway.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Timosaponin B-II suppresses gastric cancer cell proliferation and induces apoptosis via the Nrf2/miR-455-3p/KLF6 pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月23日

查看全文
  • Qiaoyan Cui,
  • Ruijie Zhang,
  • Shiqiao Zhao,
  • Jian Wang,
  • Yafen Dong,
  • Xuesong Bai,
  • Ye Chen,
  • Yan Qiu

摘要

Background

Gastric cancer (GC), known for its aggressive growth and metastasis, remains a leading cause of cancer-related mortality. Although Timosaponin B-II (TB-II) from Anemarrhena asphodeloides has shown anticancer potential, its underlying mechanisms in GC are not yet fully understood.

Methods

Our study investigates and compares the expression patterns of Kruppel-Like Factor 6(KLF6) in GC tissues across different TNM stages, while exploring its upstream regulatory factors. GC cells were treated with Timosaponin B-II (TB-II), and alterations in cell proliferation and apoptosis rates were evaluated using CCK-8 and TUNEL assays. Furthermore, the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2), miR-455-3p, and KLF6 were quantified to elucidate the mechanisms underlying TB-II’s effects. To confirm the interaction between miR-455-3p and KLF6, as well as Nrf2 and miR-455-3p, bioinformatics analysis, luciferase assays, and ChIP-PCR were conducted. Finally, protein synthesis and degradation assays were performed to explore the mechanism by which TB-II regulates the expression and activity of Nrf2.

Results

Both mRNA and protein expression levels of KLF6 were significantly lower in GC tissues compared to adjacent normal tissues. Notably, only KLF6 protein expression exhibited a decline in GC tissues from stages I to III of GC, whereas its upstream regulator, miR-455-3p, displayed the opposite trend. Treatment with TB-II markedly inhibited GC cells proliferation and induced apoptosis in a dose-dependent manner. Mechanistically, TB-II treatment upregulated the expression of Kelch-like ECH-associated protein 1(Keap1) protein, facilitating the formation of the Keap1/Nrf2 complex, which enhanced the ubiquitin-mediated degradation of Nrf2 in GC cells. Consequently, the transcriptional activation of miR-455-3p by Nrf2 was suppressed, resulting in the upregulation of the tumor suppressor KLF6. Silencing KLF6 can counteract the effects of TB-II in inhibiting proliferation and promoting apoptosis in GC cells.

Conclusion

TB-II suppresses GC cell proliferation and induces apoptosis via the Nrf2/miR-455-3p/KLF6 pathway.