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Updated: Jan 24, 2026

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
Targeting Senescence: Tianma Granule Inhibits Colorectal Cancer Progression by Modulating miR-29a-5p/P53 Signaling in
Xiaojuan Tang1, Yuan Ren2, Yongmin Li1
1Central Laboratory, Hunan Province Integrated Traditional Chinese and Western Medicine Hospital (Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine), Changsha, China.
Abstract:
Chemotherapy-induced senescence-associated tumor microenvironment (S-TME) facilitates colorectal cancer (CRC) progression. This study elucidates the mechanism by which Tianma granule (TMG), a traditional Chinese medicine formula, remodels the S-TME and inhibits CRC, specifically investigating the role of the miR-29a-5p/P53 axis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 18 bioactive components in TMG, and network pharmacology highlighted P53 as a core target. Functional assays, including Cell Counting Kit-8 (CCK-8), β-galactosidase staining, flow cytometry, wound-healing, and Transwell migration tests, were conducted using doxorubicin (DOX)-induced senescent human umbilical vein endothelial cells (HUVECs) and CRC lines. TMG suppressed CRC cell proliferation, motility, and invasiveness while promoting apoptosis. TMG reduced P53/cyclin-dependent kinase inhibitor 1A (P21) and senescence-associated secretory phenotype (SASP) factors (IL-6, IL-8, CCL20), while upregulating miR-29a-5p in senescent HUVECs. miR-29a-5p inhibition enhanced senescence and increased P53/P21/SASP, whereas P53 silencing lowered P21 and decreased miR-29a-5p, indicating mutual regulation. In azoxymethane/dextran sulfate sodium (AOM/DSS)-CRC mice, TMG reduced tumor burden and improved survival, accompanied by lower P53/P21 and restored miR-29a-5p in tissues. TMG remodels the chemotherapy-induced S-TME and suppresses CRC progression by modulating the miR-29a-5p/P53 axis, enhancing apoptosis in senescent cells, and counteracting S-TME-mediated tumor growth and metastasis. This highlights TMG's therapeutic potential.
Insights
Tianma granule (TMG) remodels the tumor microenvironment and inhibits colorectal cancer (CRC) by targeting the miR-29a-5p/P53 axis. This traditional Chinese medicine enhances apoptosis and reduces tumor growth and metastasis.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Chemotherapy induces a senescence-associated tumor microenvironment (S-TME) that promotes colorectal cancer (CRC) progression.
- Traditional Chinese Medicine (TCM) formulas offer potential therapeutic strategies for cancer treatment.
Purpose of the Study:
- To elucidate the mechanism by which Tianma granule (TMG) remodels the S-TME and inhibits CRC.
- To investigate the role of the miR-29a-5p/P53 axis in TMG's anti-CRC effects.
Main Methods:
- LC-MS/MS identified TMG components; network pharmacology pinpointed P53 as a core target.
- In vitro assays used doxorubicin-induced senescent cells and CRC lines to assess TMG effects.
- In vivo studies utilized azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse models.
Main Results:
- TMG suppressed CRC cell proliferation, migration, and invasion, while promoting apoptosis.
- TMG reduced P53/P21 expression and senescence-associated secretory phenotype (SASP) factors, upregulating miR-29a-5p in senescent cells.
- TMG treatment in mice decreased tumor burden, improved survival, and modulated the miR-29a-5p/P53 axis in tumor tissues.
Conclusions:
- TMG remodels the chemotherapy-induced S-TME and suppresses CRC progression.
- TMG exerts its effects by modulating the miR-29a-5p/P53 axis, enhancing apoptosis in senescent cells.
- TMG demonstrates therapeutic potential for CRC by counteracting S-TME-mediated tumor growth and metastasis.
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