[Multiple components in Astragalus Injection target CCL2/FOS/PPARG/CXCL8 to suppress cervical cancer progression]

To predict the functional targets and molecular mechanisms of Astragalus Injection for suppressing cervical cancer.

The overlapping targets between Astragalus Injection and cervical cancer were used to construct a protein-protein interaction network. GO functional annotation and KEGG pathway enrichment analysis were performed, and molecular docking study was conducted to evaluate the binding capacity between drug active components and the core targets. SiHa cells were treated with Astragalus Injection and the changes in cell proliferation, migration and invasion were examined. The expressions of the core targets (FOS, PPARG, CXCL8, and CCL2), key molecules in the IL-17 pathway (NF-κB p65, p-p65, STAT3, and p-STAT3), Bax, Bcl-2, caspase-3, and cleaved caspase-3 were detected in the treated cells. The changes in microfilament, mitochondrial membrane potential, cell apoptosis and membrane permeability were observed using Coomassie brilliant blue, phalloidin, JC-10 and AO/EB staining. In a mouse model bearing U14 cervical cancer xenograft, the effect of Astragalus Injection on tumor growth was observed, tumor histopathology was examined using HE staining, and CCL2, PPARG and FOS expressions were analyzed with immunohistochemistry.

Five major active components of Astragalus Injection were found to stably bind to 4 core targets (CCL2, CXCL8, FOS, and PPARG) with docking binding energies all below -5 kJ/mol. Astragalus Injection significantly inhibited the proliferation, migration and invasion of SiHa cells, disrupted cytoskeletal microfilament structure, and induced cell apoptosis, causing also significantly lowered protein levels of FOS, CXCL8, CCL2, PPARG, Bcl-2, p-p65 and p-STAT3 and increased expressions of Bax and cleaved caspase-3. In the tumor-bearing mice, Astragalus Injection significantly suppressed xenograft growth, induced tumor tissue necrosis, and reduced the expressions of CCL2, PPARG and FOS.

Astragalus Injection inhibits cervical cancer progression by downregulating multiple target proteins, damaging microfilament structure, weakening tumor cell motility and promoting apoptosis.