Evidence map›Paper›PMID 40924238›Full record

ArticleMolecular biology reports2025

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

Atena Mansouri, Parichehreh Yaghmaei, Maryam Ghobeh, Mehdi Kadivar

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Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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4 authors.

Atena MansouriDepartment of Biology, SR.C., Islamic Azad University, Tehran, Iran.
Parichehreh YaghmaeiDepartment of Biology, SR.C., Islamic Azad University, Tehran, Iran.
Maryam GhobehDepartment of Biology, SR.C., Islamic Azad University, Tehran, Iran.
Mehdi KadivarDepartment of Biochemistry, Pasteur Institute of Iran, Tehran, Iran. M_Kadivar@yahoo.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColorectal 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

resultsThis 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.

conclusionsConclusions: 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.

Indexed as

Colorectal NeoplasmsMechanistic Target of Rapamycin Complex 1Neovascularization, PathologicSirolimusSTAT5 Transcription FactorTumor MicroenvironmentAngiogenesisApoptosisCancer-Associated FibroblastsCell Line, TumorCell ProliferationCell SurvivalCoculture TechniquesHumansHuman Umbilical Vein Endothelial CellsOxidative StressMechanistic Target of Rapamycin Complex 1SirolimusSTAT5A protein, humanSTAT5 Transcription FactorTumor Suppressor ProteinsAngiogenesisApoptosisColorectal cancerRapamycinSTAT5A/TORC1 signalingTumor microenvironment

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.