Bushen Jiedu formula alleviates colorectal cancer progression through reducing lncRPPH1 in tumor-derived...

The Bushen Jiedu Formula (BSJDF) is a traditional and effective chemical prescription of traditional Chinese medicine (TCM) administered due to its anti-cancer properties, particularly in colorectal cancer (CRC).

This study proposes to explore the therapeutic benefits of BSJDF against metastasis in CRC and unravel its regulatory mechanisms related to the tumor microenvironment.

The combination of mass spectrometry and network pharmacology was used to analyze the involvement of BSJDF in anti-tumor progression. In vitro and in vivo experiments were conducted to measure the regulatory effect of BSJDF on tumor-derived extracellular vesicles (EVs), which induce the M2 polarization of macrophages and CRC metastasis. Flow cytometry, immunofluorescence, and RT-qPCR assays were employed to elucidate the mechanisms by which tumor-derived EVs induce macrophage M2-type polarization.

Network pharmacology illuminated that immune and inflammatory response pathways were involved in the beneficial effects of BSJDF on CRC. In vivo experiments indicated that BSJDF suppressed the metastasis of CRC to the liver by modulating macrophage immune infiltration. Mechanically, BSJDF inhibited CRC metastasis via modulating tumor-derived EVs that facilitate the polarization of M2 macrophages. Moreover, BSJDF suppressed the metastasis of CRC and the polarization of M2 macrophages by reducing lncRPPH1 in tumor-derived EVs.

BSJDF blocked the M2-type polarization of macrophages and prevented CRC metastasis by decreasing the expression levels of lncRPPH1 in tumor-derived EVs.