Scholarlink

Background <p>Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. The tumor microenvironment (TME), particularly the interactions between endothelial cells and cancer-associated fibroblasts (CAFs), plays a pivotal role in promoting tumor growth, angiogenesis, oxidative stress, and therapy resistance. The HUVEC–fibroblast co-culture model closely mimics stromal–endothelial interactions observed in CRC, enabling mechanistic insights not achievable in monocultures. This physiologically relevant system allows simultaneous evaluation of stromal and vascular components, providing a more accurate platform to assess therapeutic interventions.</p> Methods and results <p>This study investigated the effects of rapamycin on tumor-promoting processes in a HUVEC–fibroblast co-culture model simulating stromal interactions in CRC. Rapamycin treatment was evaluated using MTT assay, tube formation, Annexin V/PI flow cytometry, oxidative stress assays (TOS and MDA), RT-qPCR, and Western blotting. Rapamycin markedly reduced endothelial cell viability (~ 38%, <i>p</i> &lt; 0.01) and tube length (~ 45%, <i>p</i> &lt; 0.01), elevated TOS (↑1.7-fold) and MDA (↑2.1-fold) levels, and induced apoptosis (~ 48% total early and late apoptotic cells, <i>p</i> &lt; 0.05). Molecular analyses demonstrated inhibition of PI3K/AKT signaling and downregulation of STAT5A and TORC1 at both the mRNA and protein levels.</p> Conclusions <p>Conclusions: Rapamycin exerts multifaceted anti-tumor effects by disrupting CAF–endothelial interactions, suppressing angiogenesis, enhancing oxidative stress, and promoting apoptosis. These findings highlight its therapeutic potential for targeting stromal–vascular crosstalk in CRC and warrant further validation in monoculture, in vivo, and clinical settings.</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

Targeting the tumor microenvironment in colorectal cancer: the effect of Rapamycin on angiogenesis, apoptosis, and STAT5A/TORC1 signaling

  • 期刊论文

  • 发表日期：

    2025年9月8日

查看全文
  • Atena Mansouri,
  • Parichehreh Yaghmaei,
  • Maryam Ghobeh,
  • Mehdi Kadivar

摘要

Background

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. The tumor microenvironment (TME), particularly the interactions between endothelial cells and cancer-associated fibroblasts (CAFs), plays a pivotal role in promoting tumor growth, angiogenesis, oxidative stress, and therapy resistance. The HUVEC–fibroblast co-culture model closely mimics stromal–endothelial interactions observed in CRC, enabling mechanistic insights not achievable in monocultures. This physiologically relevant system allows simultaneous evaluation of stromal and vascular components, providing a more accurate platform to assess therapeutic interventions.

Methods and results

This study investigated the effects of rapamycin on tumor-promoting processes in a HUVEC–fibroblast co-culture model simulating stromal interactions in CRC. Rapamycin treatment was evaluated using MTT assay, tube formation, Annexin V/PI flow cytometry, oxidative stress assays (TOS and MDA), RT-qPCR, and Western blotting. Rapamycin markedly reduced endothelial cell viability (~ 38%, p < 0.01) and tube length (~ 45%, p < 0.01), elevated TOS (↑1.7-fold) and MDA (↑2.1-fold) levels, and induced apoptosis (~ 48% total early and late apoptotic cells, p < 0.05). Molecular analyses demonstrated inhibition of PI3K/AKT signaling and downregulation of STAT5A and TORC1 at both the mRNA and protein levels.

Conclusions

Conclusions: Rapamycin exerts multifaceted anti-tumor effects by disrupting CAF–endothelial interactions, suppressing angiogenesis, enhancing oxidative stress, and promoting apoptosis. These findings highlight its therapeutic potential for targeting stromal–vascular crosstalk in CRC and warrant further validation in monoculture, in vivo, and clinical settings.