Scholarlink

<p>Tamoxifen (Tam) has been shown to reduce estrogen receptor (ER)-positive breast cancer incidence. Limited data also suggest Tam may inhibit ER-negative lung cancer, though resistance and inflammation remain significant challenges. This study investigated the co-delivery of Tam and Celecoxib (Celx) via nano-formulations to enhance efficacy and reduce inflammation in lung cancer cells. Nano-formulations of Tam and Celx were synthesized and characterized by dynamic light scattering and transmission electron microscopy, revealing particle sizes of 94.2 ± 5.6&#xa0;nm and 68.1 ± 6.5&#xa0;nm, with low polydispersity and positive surface charges. Entrapment efficiencies were 85.6 ± 5.4% (Tam) and 94.2 ± 6.7% (Celx), with controlled drug release profiles. Co-treatment with nano-Tam and nano-Celx significantly inhibited A549 lung cancer cell proliferation in a dose- and time-dependent manner while sparing normal WI38 lung cells. The combination induced apoptosis, caused G0/G1 cell cycle arrest, and showed high cellular uptake (binding affinity: 94.9% for Tam; 80.2% for Celx). Apoptosis was supported by upregulation of TRAIL, DR4, DR5, Bax, and Caspase-8 expression levels, and downregulation of c-FLIP, JAK3, STAT3, AKT1, Bcl-2, TNF-α, IL-1β, and COX-2 levels. Molecular docking revealed moderate binding affinities of both drugs to anti-apoptotic and inflammatory targets, with Celx favoring hydrogen bonds and Tam relying on hydrophobic interactions. These findings suggest that nano-formulated Tam and Celx co-therapy may offer a promising approach to treat ER-negative lung cancer by enhancing apoptosis and reducing inflammation with minimal toxicity to normal cells.</p> Graphical Abstract <p></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

Tamoxifen and Celecoxib Nanoparticles Co-Therapy for Lung Cancer Through Modulation of JAK/STAT Pathway: an In-Vitro and Molecular Docking Study

  • 期刊论文

  • 发表日期：

    2025年10月16日

查看全文
  • Ahmed A. Abd-Rabou,
  • Hussam Y. Alharbi,
  • Majed S. Aljohani,
  • Hayat D. Zagloul,
  • Mohamed A. El-Atawy

摘要

Tamoxifen (Tam) has been shown to reduce estrogen receptor (ER)-positive breast cancer incidence. Limited data also suggest Tam may inhibit ER-negative lung cancer, though resistance and inflammation remain significant challenges. This study investigated the co-delivery of Tam and Celecoxib (Celx) via nano-formulations to enhance efficacy and reduce inflammation in lung cancer cells. Nano-formulations of Tam and Celx were synthesized and characterized by dynamic light scattering and transmission electron microscopy, revealing particle sizes of 94.2 ± 5.6 nm and 68.1 ± 6.5 nm, with low polydispersity and positive surface charges. Entrapment efficiencies were 85.6 ± 5.4% (Tam) and 94.2 ± 6.7% (Celx), with controlled drug release profiles. Co-treatment with nano-Tam and nano-Celx significantly inhibited A549 lung cancer cell proliferation in a dose- and time-dependent manner while sparing normal WI38 lung cells. The combination induced apoptosis, caused G0/G1 cell cycle arrest, and showed high cellular uptake (binding affinity: 94.9% for Tam; 80.2% for Celx). Apoptosis was supported by upregulation of TRAIL, DR4, DR5, Bax, and Caspase-8 expression levels, and downregulation of c-FLIP, JAK3, STAT3, AKT1, Bcl-2, TNF-α, IL-1β, and COX-2 levels. Molecular docking revealed moderate binding affinities of both drugs to anti-apoptotic and inflammatory targets, with Celx favoring hydrogen bonds and Tam relying on hydrophobic interactions. These findings suggest that nano-formulated Tam and Celx co-therapy may offer a promising approach to treat ER-negative lung cancer by enhancing apoptosis and reducing inflammation with minimal toxicity to normal cells.

Graphical Abstract