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Feiji Formula inhibits the migration and invasion of lung cancer cells and lung metastasis in animal models by regulating complement-related proteins CFHR5/ MBL2/C9
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Abstract:
[Abstract] Objective: To investigate the effects of Feiji Formula on the migration and invasion of lung cancer cells, as well as lung metastasis in animal models and explore its possible mechanisms. Methods: TNMplot, TCGA, and DAVID databases were used to analyze the expression of complement-related proteins (CFHR5 [complement factor H-related protein 5], MBL2 [mannose-binding lectin 2], C9 [complement component 9]) in lung metastatic tissues and their relationship with immune cell infiltration, as well as related biological processes and signaling pathways. A subcutaneous xenograft mice model was established using 2LL cells. Mice were administered 2 g/mL Feiji Formula decoction (0.2 mL per dose) via oral gavage for 21 days. The effects of Feiji Formula on the incidence of lung metastasis, the number of lung metastatic nodules, and the protein expression of CFHR5/MBL2/C9 in the lung tissues of the model mice were observed. Exosome tracing assay was performed to observe the secretion and uptake of exosomes by CTC-TJH-01 and H1299 cells. Different concentrations of Feiji Formula were applied to treat H1299 and CTC-TJH-01 cells, and its effects on cell viability, invasion, migration, and CFHR5/MBL2/C9 protein expression were detected by CCK-8, scratch healing assay,Transwell assay, and WB method. Results: Network pharmacology analysis showed that CFHR5/MBL2/C9 proteins were highly expressed in lung metastatic tissues (all P < 0.05) and were closely related to the complement system involved in immune response regulation. Compared with the control group, the Feiji Formula group demonstrated a significant reduction in the number of lung metastatic nodules (P < 0.05). Feiji Formula (0-200 μg/mL) had no significant effect on the viability of H1299 and CTC-TJH-01 cells (both P > 0.05). Both CTC-TJH-01 and H1299 cells could secrete and uptake each other's exosomes. Compared with the 0 μg/mL control group, Feiji Formula at concentrations of 50-200 μg/mL significantly inhibited the migration and invasion abilities of H1299 and CTC-TJH-01 cells (P < 0.05 or P < 0.01), and significantly reduced the protein expression levels of CFHR5 and MBL2 (P <0.05 or P <0.01). Notably, the expression level of C9 protein in CTC-TJH-01 cells increased only after treatment with 200 μg/mL Feiji Formula (P < 0.05). Conclusion: Feiji Formula can inhibit the migration and invasion of lung cancer cells as well as lung metastasis in model mice by regulating complement-associated proteins CFHR5/MBL2/C9. This effect may be related to exosome-mediated intercellular communication.
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