Abstract
Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor gene in a variety of cancers including colorectal cancer and breast cancer. However, its role and the potential mechanism in endometrial carcinoma (EC) are still unclear. The purpose of this study was to explore the effect of IGFBP-rP1 on EC cell proliferation and apoptosis and its underlying mechanism. Western blot analysis and reverse transcription-quantitative PCR were used to assess protein and gene expression levels of IGFBP-rP1 in EC cells. Overexpression of IGFBP-rP1 and/or AKT serine/threonine kinase was used to analyze their effects on cell proliferation and apoptosis of the EC cells. Co-immunoprecipitation and glutathione S transferase pull-down assays were used to analyze the interaction between IGFBP-rP1 and AKT. The expression of IGFBP-rP1 in EC cells was downregulated. Overexpression of IGFBP-rP1 inhibited the proliferation and induced apoptosis of EC cells, which were abolished by the overexpression of AKT. In addition, IGFBP-rP1 directly interacted with AKT to inhibit PI3K/AKT signaling. Additionally, M0 macrophages were induced by EC cells to differentiate into M2 macrophages, which was reversed by IGFBP-rP1. Overexpression of AKT in EC cells abolished the inhibitory effect of IGFBP-rP1 on M2 polarization. IGFBP-rP1 as an oncogenic factor inhibits M2 polarization of TAMs through PI3K/AKT signaling pathway and may be a potentially valuable target for EC therapy.