Scholarlink

Background <p>Lung cancer is a leading cause of death globally, with non-small-cell lung cancer (NSCLC) often developing resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). This study explored the efficacy and mechanism of Buddlejasaponin IV (BJS IV) from <i>Clinopodium chinense</i> var. <i>shibetchense</i> in overcoming gefitinib resistance in NSCLC cells.</p> Methods <p>Cell proliferation was determined using the sulforhodamine B (SRB) assay. Mechanistic studies involved small interfering RNA (siRNA) and western blot analysis. Cell cycle and apoptosis were analyzed by flow cytometry. The impact of BJS IV on epithelial–mesenchymal transition (EMT) was evaluated through cell invasion and wound-healing assays. Angiogenesis was assessed via tube formation assay and real-time polymerase chain reaction (PCR). Drug combination efficacy was tested by the Chou–Talalay method.</p> Results <p>BJS IV inhibited proliferation in HCC827 and HCC827-gef cells with IC<sub>50</sub> values of 4.50 µM and 7.84 µM, respectively. It suppressed activated signal transducer and activator of transcription (p-STAT3) in HCC827-gef cells, and STAT3 inhibition by siRNA restored gefitinib sensitivity. Long-term BJS IV exposure induced apoptosis by downregulating B-cell lymphoma-extra-large (Bcl-xL) and Bcl-2 and upregulating cleaved caspase 3, cleaved caspase 9 and cleaved poly (ADP-ribose) polymerase (PARP) in HCC827-gef cells. BJS IV also inhibited migration and invasion by downregulating EMT markers N-cadherin, snail, and vimentin. It significantly suppressed vascular endothelial growth factor (VEGF) expression in HCC827-gef cells, inhibiting angiogenesis in VEGF-induced tube formation in HUVECs. Combined BJS IV and gefitinib treatment showed synergistic antiproliferative effects in HCC827-gef cells.</p> Conclusions <p>BJS IV demonstrated potential antiproliferative activity via STAT3 suppression and apoptosis induction. BJS IV also inhibited migration, invasion, EMT transition, and angiogenesis in HCC827-gef cells, suggesting BJS IV as a potential therapeutic agent for overcoming gefitinib resistance in NSCLC.</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

Buddlejasaponin IV inhibits proliferation and migration via STAT3 suppression in gefitinib-resistant non-small cell lung cancer cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月11日

查看全文
  • Sung Chul Jang,
  • Donghwa Kim,
  • Jaeho Han,
  • Dong Hyun Moon,
  • Eun Seo Bae,
  • Chae Won Ock,
  • Hyen Joo Park,
  • Sang Kook Lee

摘要

Background

Lung cancer is a leading cause of death globally, with non-small-cell lung cancer (NSCLC) often developing resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). This study explored the efficacy and mechanism of Buddlejasaponin IV (BJS IV) from Clinopodium chinense var. shibetchense in overcoming gefitinib resistance in NSCLC cells.

Methods

Cell proliferation was determined using the sulforhodamine B (SRB) assay. Mechanistic studies involved small interfering RNA (siRNA) and western blot analysis. Cell cycle and apoptosis were analyzed by flow cytometry. The impact of BJS IV on epithelial–mesenchymal transition (EMT) was evaluated through cell invasion and wound-healing assays. Angiogenesis was assessed via tube formation assay and real-time polymerase chain reaction (PCR). Drug combination efficacy was tested by the Chou–Talalay method.

Results

BJS IV inhibited proliferation in HCC827 and HCC827-gef cells with IC50 values of 4.50 µM and 7.84 µM, respectively. It suppressed activated signal transducer and activator of transcription (p-STAT3) in HCC827-gef cells, and STAT3 inhibition by siRNA restored gefitinib sensitivity. Long-term BJS IV exposure induced apoptosis by downregulating B-cell lymphoma-extra-large (Bcl-xL) and Bcl-2 and upregulating cleaved caspase 3, cleaved caspase 9 and cleaved poly (ADP-ribose) polymerase (PARP) in HCC827-gef cells. BJS IV also inhibited migration and invasion by downregulating EMT markers N-cadherin, snail, and vimentin. It significantly suppressed vascular endothelial growth factor (VEGF) expression in HCC827-gef cells, inhibiting angiogenesis in VEGF-induced tube formation in HUVECs. Combined BJS IV and gefitinib treatment showed synergistic antiproliferative effects in HCC827-gef cells.

Conclusions

BJS IV demonstrated potential antiproliferative activity via STAT3 suppression and apoptosis induction. BJS IV also inhibited migration, invasion, EMT transition, and angiogenesis in HCC827-gef cells, suggesting BJS IV as a potential therapeutic agent for overcoming gefitinib resistance in NSCLC.