SOX7 inhibits colorectal cancer proliferation，invasion and migration through the SHP-2 / Wnt / β-catenin / ROS pathway
10.19405/j.cnki.issn1000-1492.2024.07.020
- Author:
Xueliang Wu
1
;
Likun Wang
2
;
Hongqing Ma
3
;
Shaodong Li
4
;
Yan Liang
4
;
Zhilong Hui
4
;
Lei Han
4
;
Jun Xue
4
Author Information
1. Dept of General Surgery，The First Affiliated Hospital of Hebei North University，Zhangjiakou 075000；Institute of Cancer，The First Affiliated Hospital of Hebei North University，Zhangjiakou 075000
2. Dept of Ultrasound， The First Affiliated Hospital of Hebei North University，Zhangjiakou 075000
3. Dept of Surgery，The Fourth Hospital of Hebei Medical University，Shijiazhuang 050000
4. Dept of General Surgery，The First Affiliated Hospital of Hebei North University，Zhangjiakou 075000
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
SOX7;
ROS;
SHP-2;
Wnt / β-catenin;
proliferation;
invasion;
migration
- From:
Acta Universitatis Medicinalis Anhui
2024;59(7):1237-1243
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the molecular mechanisms by which SOX7 regulates the SHP-2 / Wnt / β-cate- nin / ROS pathway，affecting the proliferation，invasion，and migration of colorectal cancer cells．
Methods :Twenty nude mice with subcutaneously transplanted tumor models were randomly divided into four groups : SOX7 NC (n = 5) ，SOX mimic (n = 5) ，SOX7 NC + PHPS1 (n = 5) ，and SOX7 mimic + PHPS1 (n = 5) to observe tumor growth. Human colorectal cancer cell line SW480 cells were transfected via lipofection and divided into six groups : SOX7 NC，SOX7 mimic，SOX7 NC + H2 O2 ，SOX7 mimic + H2 O2 ，SOX7 NC + PHPS1，and SOX7 mimic + PHPS1．The ex- pression of SHP-2 / Wnt / β-catenin / ROS pathway-related proteins in SW480 cells of each group was detected by Western blot．The invasion and migration capabilities of SW480 cells were assessed through scratch and Transwell invasion assays，while cell proliferation was evaluated using CCK-8 .
Results :In vivo experiments demonstrated that tumors in the SOX7 mimic group were significantly smaller than those in the SOX7 NC group (P＜0. 01) ．Tumors treated with PHPS1 intervention exhibited a significant increase in volume．There was no statistical significance in the difference in tumor volume between the SOX7 mimic + PHPS1 group and the SOX7 NC + PHPS1 group．In vitro experiments revealed that SOX7 mimic inhibited the expression of Wnt，β-catenin，NOX2，NOX4，PI3K，P-PI3K， AKT，P-AKT proteins (P ＜0. 01) ，and promoted the expression of p-SHP-2 protein (P ＜0. 01 ) ．The addition of hydrogen peroxide and SHP-2 inhibitor reversed the effects of SOX7 on SW480 cells (P＜0. 05) ，and significantly promoted the expression levels of Wnt，β-catenin，NOX2，NOX4，PI3K，P-PI3K，AKT，P-AKT proteins，with no sig- nificant difference，while significantly reducing the expression levels of SHP-2，p-SHP-2 proteins，with no significant difference．PHPS1 inhibited the expression of SHP-2，p-SHP-2 proteins (P＜0. 05) and upregulated the expression of Wnt，β-catenin，NOX2，NOX4，PI3K，P-PI3K，AKT，P-AKT proteins (P＜0. 05) ．Scratch，Transwell invasion and migration assays，and CCK-8 experiments indicated that SOX7 suppressed the migration，invasion，and proliferation of SW480 cells through oxidative stress and the SHP-2 pathway (P ＜0. 01) ，while H2 O2 and PHPS1 intervention promoted the migration，invasion，and proliferation of SW480 cells (P ＜0. 05 ) ．
Conclusion :SOX7 can suppress the proliferation，invasion，and migration of colorectal cancer by targeting the SHP-2 / Wnt / β-catenin / ROS pathway.
- Full text:2024091410390129838SOX7通过靶向调控SHP...直肠癌细胞增殖、侵袭和迁移_武雪亮.pdf
