Spermidine-mediated AMPK signaling pathway drives M2 macrophage polarization to promote the growth of vaginal cancer

Abstract

Vaginal cancer represents a rare and malignant tumor in the reproductive tract, with its mechanisms of onset and progression still uncharted. Spermidine (SPD), with its anti-inflammatory biological properties, has been connected to metabolic irregularities in a range of diseases. However, the specific molecular pathways through which SPD may impact the growth of vaginal cancer are not well understood. Consequently, this study delved into the biological effects of SPD within the context of vaginal cancer. Vaginal swabs from healthy individuals and vaginal cancer patients were acquired to quantify SPD levels with an enzyme-linked immunosorbent assay. The effects of supplemental exogenous SPD on vaginal cancer cell viability were examined by the cell counting kit-8 test. The impact of SPD treatment on macrophage polarization was appraised via qRT-PCR and flow cytometry. The expression of AMPK and mTOR, proteins within the AMPK/mTOR signaling pathway, was analyzed in macrophages using the western blot. Elevated levels of SPD were found in vaginal cancer patient samples. The treatment with SPD led to increased phosphorylation levels of AMPK and mTOR proteins within macrophages, thereby activating the AMPK/mTOR signaling pathway. Such treatment also promoted the expression of markers associated with M2 polarization and inhibited those related to M1 polarization. The introduction of an AMPK pathway inhibitor counteracted these results. SPD, which is present at higher levels in vaginal cancer patients, can activate the AMPK/mTOR signaling pathway and induce macrophage M2 polarization that promotes the growth of vaginal cancer cells.