PHPS1 enhances PD-L1 serine phosphorylation by regulating ROS/SHP-2/AMPK activity to promote apoptosis of oral squamous cell carcinoma cells.
10.12122/j.issn.1673-4254.2024.12.24
- Author:
Jinhong ZHANG
1
;
Xin LIU
2
;
Jian LIU
2
Author Information
1. Department of Stomatology, First Hospital of Hebei Medical University, Shijiazhuang 050031, China.
2. Department of Stomatology, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
- Publication Type:Journal Article
- Keywords:
PD-L1;
SHP-2;
mitogen-activated protein kinase;
oral squamous cell carcinoma
- MeSH:
Animals;
B7-H1 Antigen/metabolism*;
Apoptosis/drug effects*;
Mice;
Carcinoma, Squamous Cell/pathology*;
Cell Line, Tumor;
Mouth Neoplasms/pathology*;
Mice, Nude;
Humans;
AMP-Activated Protein Kinases/metabolism*;
Phosphorylation;
Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism*;
Reactive Oxygen Species/metabolism*;
Neovascularization, Pathologic/metabolism*;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
- From:
Journal of Southern Medical University
2024;44(12):2469-2476
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the mechanism of PHPS1 for promoting apoptosis of oral squamous cell carcinoma cells and the role of AMPK in regulating tumor angiogenesis under hypoxic conditions.
METHODS:Human oral squamous cell carcinoma Ca9-22 cells cultured in hypoxic conditions (1% O2) were inoculated subcutaneously in 16 nude mice, which were divided into control group and PHPS1 group (n=8) for treatment with 10% DMSO and 10% PHPS1 respectively. Tumor growth in the mice was monitored till 14 days after the treatment, and the xenografts were examined pathologically using HE staining. In Ca9-22 cells cultured in 1% O2, the effect of PHPS1, compound C (an AMPK inhibitor), and their combination on expressions of SHP-2, AMPK, HIF-1α, PD-L1, caspase-8, caspase-3 and BAX were evaluated using Western blotting.
RESULTS:In the tumor-bearing nude mice, PHPS1 treatment significantly inhibited tumor growth and neovascularization. HE staining showed significantly reduced tumor angiogenesis in PHPS1-treated mice. In Ca9-22 cells in hypoxic cultures, PHPS1 treatment significantly decreased the expression levels of SHP-2, HIF-1α, PD-L1, ERK2, STAT3 and VEGF and increased the expression of AMPK. The inhibitory effects of PHPS1 on HIF-1α and PD-L1 were obviously attenuated by the addition of compound C. PHPS1 also enhanced the expressions of caspase-3, caspase-8 and Bax proteins and increased the phosphorylation levels of PD-L1 and S195 in Ca9-22 cells, and these effects were effectively attenuated by compound C.
CONCLUSIONS:PHPS1 can enhance PD-L1 serine phosphorylation by regulating SHP-2/AMPK activity to promote apoptosis of oral squamous cell carcinoma cells under hypoxic conditions.
