Abstract
Gastric cancer (GC) remains among the leading causes of cancer-related mortality worldwide. Chronic alcohol consumption is a known risk factor for GC, but direct experimental evidence supporting alcohol as an independent oncogenic driver remains insufficient. In this study, we established a subcutaneous xenograft tumor model in nude mice by injecting MKN-45 cells and utilizing phorbol-12-myristate-13-acetate (PMA) to differentiate THP-1 cells into M0 macrophages. MKN-45 cells were then cultured with conditioned medium from alcohol-treated macrophages to evaluate malignant behaviors. Our findings demonstrate that alcohol consumption accelerated tumor growth in nude mice and increased the expression of Ki67 and epithelial‒mesenchymal transition (EMT) markers (N-cadherin and vimentin) but decreased the expression of E-cadherin. Furthermore, alcohol suppressed the expression of M1 macrophage polarization markers (iNOS, CD16, and CD86) and increased the expression of M2 markers (Arg1, CD163, and CD206), thereby promoting GC cell proliferation and migration. Notably, the expression of miR-29c-3p was downregulated in the blood of patients with GC who consumed alcohol and in the tumor tissues of alcohol-exposed mice. The overexpression of miR-29c-3p in macrophages reversed alcohol-induced effects by promoting M1 polarization and inhibiting M2 polarization. Mechanistically, alcohol suppresses miR-29c-3p expression in macrophages, leading to increased COL1A1 expression, which drives M2 polarization and accelerates GC progression.
Supplementary information:
The online version contains supplementary material available at 10.1007/s10616-025-00862-z.
Keywords:
Alcohol consumption; COL1A1; Gastric cancer; Macrophage M2 polarization; MiR-29c-3p.