ABSTRACT
Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years， studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis， skin diseases， diabetes， coronary heart disease， breast cancer， colorectal cancer， and lung cancer， especially the metastasis of malignancies and drug resistance， through multiple signaling pathways， including nuclear factor kappa-B（NF-κB）， c-Jun N-terminal kinase（JNK）， protein kinase B （Akt）， mitogen-activated protein kinase （MAPK）， signal transducer and activator of transcription 6 （STAT6）， Wnt/β-catenin， and mammalian target of rapamycin （mTOR） and regulatory factors， such as granulocyte-macrophage colony-stimulating factor （GM-CSF）， interleukin （IL）-4， IL-10， transforming growth factor （TGF）-β， tumor necrosis factor（TNF）-α， and interferon-γ（IFN-γ）. Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years， therefore， the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation， apoptosis， and metastasis of tumor cells. Therefore， targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years， this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives， i.e.， macrophage polarization， related pathways and regulatory factors of macrophage polarization， macrophage polarization and breast cancer， colorectal cancer， and lung cancer， and macrophage polarization and anti-tumor effects of Chinese medicine， active ingredients of Chinese medicine， and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment， basic research， and development of new Chinese medicine in the treatment of tumors.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the antiproliferative and anti-metastasis effect of Xihuang Pill (, XP) on human colorectal cancer cell and to explore the molecular mechanism by which it produces the effects.</p><p><b>METHODS</b>Highly metastatic human colorectal cancer cell line LoVo was treated with low-, medium-, and highdose XP-containing serum (XP-L, XP-M, XP-H) groups for 48 h, cells intervened with no drug rat serum and PD98059 [extracellular signal-regulated kinase (ERK) inhibitor] as negative and positive controls (NC and PC) groups. Cell proliferation assay was made using cell counting kit-8 (CCK8). The 8 μm pore-size transwell chamber and 4', 6-diamidino-2-phenylindole (DAPI) staining were applied to examine the ability of invasion and migration of the cells. The protein expression of ERK1/2, zinc fifi nger E-box-binding homeobox 1 (ZEB1), Scrib and lethal giant larvae homolog 2 (Lgl2) was detected by Western blotting while the relative mRNA quantity of E-cadherin, N-cadherin, Occludin and junctional adhesion molecule-1 (JAM1) was measured by realtime fluorescent quantitative polymerase chain reaction (RT-qPCR).</p><p><b>RESULTS</b>XP induced a dose-dependent suppression on the proliferation of LoVo cells (P <0.05 or P<0.01), with the inhibition rates varied from 27.30% to 31.08%. Transwell assay showed that when preprocessed with PD98059 and XP-containing serum, the number of cells that passed the filter decreased significantly compared with that of NC group (P <0.05 or P<0.01). Moreover, XP inhibited the protein expression of ERK1/2 and ZEB1 (P <0.05); and up-regulated the protein expression of Scrib and Lgl2 (P <0.05). The mRNA levels of E-cadherin, Occludin and JAM1 of the XP intervened groups and PC group markedly ascended (P <0.05) while that of N-cadherin showed a descending tendency (P>0.05).</p><p><b>CONCLUSION</b>XP intervention suppressed the ability of proliferation, invasion and migration of the LoVo cells. Regulating ZEB1-SCRIB Loop so as to recover epithelial phenotype and apical junctional complex might be one of the mechanisms by which XP produces the anti-metastasis effect.</p>