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Mitogen-activated protein kinase inhibitor PD0325901 enhances radiosensitivity by modulating PD-1/PD-L1 through MEK/ERK pathway in cervical cancer cells
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Q. Qin   , C. Liu , J. Lu , J. Wang , Z. Li |
| Department of Gynaecology and Obstetrics, The Second Clinical Medical College, China Three Gorges University, Yichang 443001, Hubei Province, China , teng.prof@gmail.com |
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Abstract: (665 Views) |
Background: To investigate the mechanism of mitogen-activated protein kinase (MEK) inhibitor PD0325901-mediated MEK/extracellular signal-regulated kinase (ERK1)/2 pathway on programmed death-1(PD-1) and ligand programmed death ligand-1(PD-L1) in cervical cancer (CC) cells. Materials and Methods: CC HeLa cells were divided into three groups: control (Group A), PD0325901 (100 nmol/L) (Group B), and Phorbol 12-myristate 13-acetate (PMA) (100 nmol/L PD0325901 + 10 μmol/L PMA) (Group C). The methodology used for simulation radiotherapy includes assessing cell viability at 12h and 24h using3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by Annexin V-FITC/PI method, invasion through Transwell assay, and gene expression by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. PD0325901 was tested as a potential radiosensitizer by modulating PD-1/PD-L1 immune checkpoint expression and affecting the MEK/ERK pathway in simulated post-radiotherapy conditions. Results: At 12h and 24h, cell viability in Group B was significantly lower than Group A, with increased apoptosis rates in Group B compared to Group A. Group C showed partial reversal of these effects. MEK/ERK1/2, PD-1, and PD-L1 expression were reduced in Group B, but upregulated in Group C, confirming the impact of PD0325901 on immune checkpoint modulation. Conclusion: PD0325901 inhibits the MEK/ERK1/2 pathway, leading to suppression of PD-1/PD-L1 expression and enhanced apoptosis in cervical cancer cells, suggesting a potential role for PD0325901 in enhancing radiosensitivity by modulating immune checkpoint signaling. |
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| Keywords: Cervical cancer, MEK inhibitor, PD0325901, MEK/ERK pathway, PD-1/PD-L1, radiosensitization, apoptosis. |
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Full-Text [PDF 795 kb]
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Subject:
Radiation Biology
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