Gao Juan, Suo Shiqi, Li Jingxia, Wang Chunxia, Deng Ranran, Hu Yuxia, Zhang Chunzheng
Department of Gynecology, Affiliated Hospital of Hebei Engineering University, Handan, Hebei 056001, P.R. China.
Department of Obstetrics, Handan First Hospital, Handan, Hebei 056002, P.R. China.
Exp Ther Med. 2023 Mar 3;25(4):169. doi: 10.3892/etm.2023.11868. eCollection 2023 Apr.
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.
胰岛素样生长因子结合蛋白相关蛋白1（IGFBP-rP1）在包括结直肠癌和乳腺癌在内的多种癌症中是一种潜在的肿瘤抑制基因。然而，其在子宫内膜癌（EC）中的作用及潜在机制仍不清楚。本研究的目的是探讨IGFBP-rP1对EC细胞增殖和凋亡的影响及其潜在机制。采用蛋白质免疫印迹分析和逆转录定量PCR评估EC细胞中IGFBP-rP1的蛋白质和基因表达水平。通过过表达IGFBP-rP1和/或AKT丝氨酸/苏氨酸激酶来分析它们对EC细胞增殖和凋亡的影响。采用免疫共沉淀和谷胱甘肽S转移酶下拉实验分析IGFBP-rP1与AKT之间的相互作用。EC细胞中IGFBP-rP1的表达下调。过表达IGFBP-rP1抑制了EC细胞的增殖并诱导其凋亡，而AKT的过表达消除了这些作用。此外，IGFBP-rP1直接与AKT相互作用以抑制PI3K/AKT信号传导。另外，EC细胞诱导M0巨噬细胞分化为M2巨噬细胞，而IGFBP-rP1可逆转这一过程。EC细胞中过表达AKT消除了IGFBP-rP1对M2极化的抑制作用。IGFBP-rP1作为一种致癌因子，通过PI3K/AKT信号通路抑制肿瘤相关巨噬细胞的M2极化，可能是EC治疗中一个潜在的有价值靶点。
