戊二脒通过 PI3K/AKT 信号通路抑制子宫内膜癌细胞的增殖、迁移和侵袭。

Pentamidine inhibits proliferation, migration and invasion in endometrial cancer via the PI3K/AKT signaling pathway.

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin City, 150001, Heilongjiang Province, People's Republic of China.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin City, 150001, Heilongjiang Province, People's Republic of China.

出版信息

BMC Womens Health. 2022 Nov 24;22(1):470. doi: 10.1186/s12905-022-02078-1.

DOI:10.1186/s12905-022-02078-1

PMID:36434592

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9700983/

Abstract

BACKGROUND

Pentamidine has been reported to have many pharmacological effects including anti- protozoal, anti-inflammatory, and anti-tumor activities. The aim of this study is to investigate the potential therapeutic role of Pentamidine and molecular mechanisms of Pentamidine on PI3K/AKT signaling pathway underlying the anti-tumor properties in endometrial cancer.

METHODS

Our study was carried out in the central laboratory of Harbin Medical University from 2019 to 2021. Human endometrial cancer cell lines Ishikawa and HEC-1A were treated with Pentamidine. The proliferation ability of cells was investigated by MTS and colony formation assays. The cell cycle distribution was detected by flow cytometry. Cell migration and invasion were analyzed by using the wound healing assay and Transwell assay. Western blotting was performed to measure the levels of AKT, p-AKT, MMP-2, and MMP-9.

RESULTS

Our results revealed that treatment of Pentamidine inhibited proliferation, migration and invasion of Ishikawa and HEC-1A endometrial cancer cells. Mechanistic investigation showed that Pentamidine inhibited PI3K/AKT signaling pathway and also reduced the expression of MMP-2 and MMP-9. In addition, co-treatment with PI3K kinase inhibitor LY294002 and Pentamidine leaded to increased repression of cell viability and the protein expression of p-AKT in Ishikawa cells.

CONCLUSIONS

Pentamidine suppresses PI3K/AKT signaling pathway, and inhibits proliferation, migration and invasion of EC cells. These findings suggested that Pentamidine might be a potential candidate for treating EC through PI3K/AKT pathway.

摘要

背景

戊二脒已被报道具有许多药理学作用，包括抗原生动物、抗炎和抗肿瘤活性。本研究旨在探讨戊二脒在子宫内膜癌中抗肿瘤特性的潜在治疗作用及其对 PI3K/AKT 信号通路的分子机制。

方法

本研究于 2019 年至 2021 年在哈尔滨医科大学中心实验室进行。用人子宫内膜癌细胞系 Ishikawa 和 HEC-1A 处理戊二脒。通过 MTS 和集落形成实验研究细胞的增殖能力。通过流式细胞术检测细胞周期分布。使用划痕愈合实验和 Transwell 实验分析细胞迁移和侵袭。通过 Western blot 测定 AKT、p-AKT、MMP-2 和 MMP-9 的水平。

结果

我们的结果表明，戊二脒处理抑制了 Ishikawa 和 HEC-1A 子宫内膜癌细胞的增殖、迁移和侵袭。机制研究表明，戊二脒抑制了 PI3K/AKT 信号通路，并降低了 MMP-2 和 MMP-9 的表达。此外，PI3K 激酶抑制剂 LY294002 和戊二脒共同处理导致 Ishikawa 细胞中细胞活力和 p-AKT 蛋白表达的抑制增加。