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.

PubMed

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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