Network pharmacology-based investigation of the effects of Shenqi Fuzheng injection on glioma proliferation and migration via the SRC/PI3K/AKT signaling pathway

Abstract

Ethnopharmacological relevance: In the clinic, Shenqi Fuzheng Injection (SFI) is used as an adjuvant for cancer chemotherapy. However, the molecular mechanism is unclear.

Aim of the study: We screened potential targets of SFI action on gliomas by network pharmacology and performed experiments to validate possible molecular mechanisms against gliomas.

Materials and methods: We consulted relevant reports on the SFI and glioma incidence from PubMed and Web of Science and focused on the mechanism through which the SFI inhibits glioma. According to the literature, two primary SFI components-Codonopsis pilosula (Franch.) Nannf. and Astragalus membranaceus (Fisch.) Bunge-have been found. All plant names have been sourced from "The Plant List" (www.theplantlist.org). The cell lines U87, T98G and GL261 were used in this study. The inhibitory effects of SFI on glioma cells U87 and T98G were detected by CCK-8 assay, EdU, plate cloning assay, scratch assay, Transwell assay, immunofluorescence, flow cytometry and Western blot. A subcutaneous tumor model of C57BL/6 mice was constructed using GL261 cells, and the SFI was evaluated by HE staining and immunohistochemistry. The targets of glioma and the SFI were screened using network pharmacology.

Results: A total of 110 targets were enriched, and a total of 26 major active components in the SFI were investigated. There were a total of 3,343 targets for gliomas, of which 79 targets were shared between the SFI and glioma tissues. SFI successfully prevented proliferation and caused cellular S-phase blockage in U87 and T98G cells, thus decreasing their growth. Furthermore, SFI suppressed cell migration by downregulating EMT marker expression. According to the results of the in vivo tests, the SFI dramatically decreased the development of tumors in a transplanted tumour model. Network pharmacological studies revealed that the SRC/PI3K/AKT signaling pathway may be the pathway through which SFI exerts its anti-glioma effects.

Conclusions: The findings revealed that the SRC/PI3K/AKT signaling pathway may be involved in the mechanism through which SFI inhibits the proliferation and migration of glioma cells.

Keywords: Glioma; Network pharmacology; SRC/PI3K/AKT pathway; Shenqi Fuzheng injection.