Isthmin-1 suppresses the growth of non-small cell lung cancer by regulating the FoxO signaling pathway
10.11665/j.issn.1000-5048.2025042102
- VernacularTitle:Isthmin-1通过调控FoxO信号通路抑制非小细胞肺癌细胞生长的研究
- Author:
Liying WANG
1
;
Xin ZHOU
;
Xuerong WANG
;
Wenbin HUANG
Author Information
1. 南京医科大学基础医学院药理学系, 南京 211166;南京医科大学基础医学院病理学系, 南京 211166;河南科技大学第一附属医院病理科, 洛阳 471003
- Publication Type:Journal Article 期刊文章
- Keywords:
non-small cell lung cancer;
isthmin-1;
FoxO signaling pathway;
apoptosis;
reactive oxygen species
- From:
Journal of China Pharmaceutical University
2026;57(1):60-67
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effects of the peptide secreted protein isthmin-1 (ISM1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells. ISM1 expression in NSCLC was detected by immunohistochemistry (IHC). ISM1 was overexpressed in lung cancer cell lines by transient transfection of ISM1 plasmids, or establishing ISM1 overexpression stable cell lines, or by treating cells with recombined ISM1 (rISM1). CCK-8 was used to examine cell growth. The intracellular signal transduction pathways regulated by rISM1 were analyzed by transcriptome sequencing, and verified by qRT-PCR and Western blot. The levels of intracellular ROS and apoptosis were further detected using the kit. The results showed that the expression of ISM1 was decreased in human NSCLC tissue samples compared to normal lung tissue samples. Overexpression of ISM1 or rISM1 treatment significantly suppressed the growth of lung cancer cells. RNA sequencing revealed that rISM1 mainly regulated the FoxO signaling pathway. rISM1 treatment decreased the expression of FoxO3 and FoxO1, increased reactive oxygen species (ROS) production, and induced cell apoptosis. These results suggest that ISM1 can inhibit the growth of NSCLC by regulating the FoxO signaling pathway. These findings provide new strategies for cancer therapy.
