Table 4.
Synthetic agents derived from natural products and combination strategies targeting TAMs in colon cancer.
| Drug | Pharmacological function | Combination agent | In vivo model and administration dose | In vitro model | Effect on macrophages | Anti-tumor function | Ref. |
|---|---|---|---|---|---|---|---|
| Aspirin | antiplatelet, anti-inflammation, antipyretic | / | AOM/DSS, AOM mice: 25, 50 mg/kg | / | ↓ macrophages infiltration, iNOS | inhibit tumorgenesis, inflammation, angiogenesis | (193) |
| Fenretinide | anticancer, chemoprevention, retinal protection | / | APCmin/+ mice: 20mg/kg | RAW264.7 HCT116, SW260, SW480, Colo205 |
↓M2 polarization, Fizz1, PPAR-γ, p-STAT6 | inhibit tumorgenesis, angiogenesis | (194) |
| Plinabulin | anticancer, immune modulation, anti-angiogenesis | / | C57BL/6N mice: MC38 subcutaneous inoculation, 7mg/kg | PBMC, BMDM MC38 Hut78 |
↑ M1 polarization, IL-1β, IL-6, IL12p40, ↓ IL-10, IL-4, ↑ active JNK pathway, Fas-L | inhibit tumor growth, induce tumor cell death through Fas/Fas-L pathway | (195) |
| Mannose-methyl-β-cyclodextrin | anticancer, immune modulation | / | BALB/c male mice: colon-26 subcutaneous inoculation, 10mg/kg | RAW264.7 Colon-26 |
↓ the amount of M2, ↑ intracellular uptake via MR | inhibit tumor growth, promote tumor cell autophagy | (196) |
| (Z)-1-(3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)-3-(isoxazol-3-yl)urea derivatives, compound 21 | anticancer | / | C57BL/6 mice: MC38 subcutaneous inoculation, 5, 10, 20mg/kg | THP-1 MC38, HCT116 |
↓ M2 polarization, IL-10, ARG1, CHIL3, VEGF, ↑ IL-12, TNF-α, IL-6, ↓ CSF-1R | inhibit tumor growth through suppressing CSF-1R and p-AKT signaling | (197) |
| Astragaloside IV | immune modulation, anti-inflammatory, antioxidant | aPD-1 | BALB/c female mouse: CT26 axillary fat pad injection, Astragaloside IV: 15 mg/kg, aPD-1: 2.5mg/kg | BMDM CT26 |
↑ M1 polarization, IFN-γ, IL-12, TNF-α, ↓ Arg1, TGF-β, IL-10, VEGF-A | inhibit tumor growth | (184) |
| the sesquiterpene lactone-rich fraction of I. helenium (SFIH) | anticancer, anti-inflammation, immune modulation | aPD-1 | C57BL/6 female mice: MC38 subcutaneous inoculation, SFIH: 50mg/kg, aPD-1: 200μg | / | ↑ M1 infiltration | inhibit tumor growth, activate adaptive immune response | (198) |
| Lobeline | anticancer, neuroregulatory effect | aPD-1 | C57BL/6 mice: MC38 subcutaneous inoculation, Lobeline: 25mg/kg, aPD1: 5mg/kg | / | ↑ M1 polarization, ↓ M2 polarization | inhibit tumor growth through regulating MAPK14/p53/Slurp1 signaling pathway, activate adaptive immune response | (149) |
| Imprime PGG | anticancer, immune modulation | aPD-1 | C57BL/6 mice: MC38 subcutaneous inoculation, Imprime: 1.2mg, aPD-1: 0.1mg | / | ↑ M1 polarization, TNF-α, PD-L1, | inhibit tumor growth, activate NK cells and DC cells, promote T cells expansion | (199) |
| Chinese yam polysaccharide (CYP) | hypoglycemic, hypolipidemic, immune modulation | aPD-1 | C57BL/6 mice: MC38 intraperitoneal injection, BALB/c mice: CT26 intraperitoneal injection, CYP: 100 mg/kg, aPD-1: 200 μg | / | ↓ M2 polarization, ARG1, IL-10 | inhibit tumor growth, regulate intestinal microbiota-related metabolites, reprogram TME | (200) |
| 7S,15R-Dihydroxy-16S,17S-Epoxy-Docosapentaenoic Acid (diHEP-DPA) | anticancer, retinal protection, lipid metabolism regulation | 5-FU | BALB/c female mice: CT26 xenograft, diHEP-DPA: 10, 20μg/kg, 5-FU: 20mg/kg | THP-1 HT29, HCT116 |
↓ M2 infiltration, MMP2, MMP9, VEGF, IL-6, TNF-α, NF-κB signaling pathway, ↑ phagocytic activity via CD47/SIRPα axis | inhibit tumor growth, EMT, inhibit cancer stem cells activation through ROS/STAT3 signaling pathway | (201, 202) |
| Ovatodiolide | anticancer, anti-inflammation | 5-FU | BALB/c mice: CT26 xenograft, Ovatodiolide: 5mg/kg, 5-FU: 30mg/kg | THP-1 HCT116, DLD-1 |
↓ M2 polarization, ARG1, CD23, YAP1, β-catenin, AKT, NF-κB, IL-6 | inhibit tumorigenesis and colon sphere generation | (203) |