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.
Tang et al. (Thu,) studied this question.