Effects of p38 phosphorylation on stemness maintenance and chemotherapy drug resistance of PANC-1 cells.
- Author:
Xueying SHI
1
;
Jinbo YU
1
;
Shihai YANG
2
;
Jin ZHAO
3
,
4
Author Information
1. The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China.
2. The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China. *Corresponding authors, E-mail: 421840752@qq.com.
3. The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou 014010, China. *Corresponding authors, E-mail: zhaojin20072008@
4. com.
- Publication Type:Journal Article
- MeSH:
Humans;
Phosphorylation/drug effects*;
Cell Line, Tumor;
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors*;
Neoplastic Stem Cells/metabolism*;
Drug Resistance, Neoplasm/drug effects*;
Fluorouracil/pharmacology*;
Pancreatic Neoplasms/pathology*;
Apoptosis/drug effects*;
SOXB1 Transcription Factors/genetics*;
Octamer Transcription Factor-3/genetics*
- From:
Chinese Journal of Cellular and Molecular Immunology
2025;41(2):116-124
- CountryChina
- Language:Chinese
-
Abstract:
Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC50, IC50, and 2×IC50) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44+CD133+PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44+CD133+cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
