International Journal of Radiation Research

en Mitogen-activated protein kinase inhibitor PD0325901 enhances radiosensitivity by modulating PD-1/PD-L1 through MEK/ERK pathway in cervical cancer cells Radiation Biology Radiation Biology <div style="text-align: justify;">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.</div> Cervical cancer, MEK inhibitor, PD0325901, MEK/ERK pathway, PD-1/PD-L1, radiosensitization, apoptosis. 365 371 http://ijrr.com/browse.php?a_code=A-10-1-1504&slc_lang=en&sid=1 Q. Qin 7900319475328460033469 7900319475328460033469 No Department of Gynaecology and Obstetrics, The Second Clinical Medical College, China Three Gorges University, Yichang 443001, Hubei Province, China C. Liu 7900319475328460033470 7900319475328460033470 No Tumor Microenvironment and Immunotherapy, Hubei Key Laboratory, China Three Gorges University, Yichang 443002, Hubei Province, China J. Lu 7900319475328460033471 7900319475328460033471 No Department of Gynaecology and Obstetrics, The Second Clinical Medical College, China Three Gorges University, Yichang 443001, Hubei Province, China J. Wang 7900319475328460033472 7900319475328460033472 No Department of Gynaecology and Obstetrics, The Second Clinical Medical College, China Three Gorges University, Yichang 443001, Hubei Province, China Z. Li teng.prof@gmail.com 7900319475328460033473 7900319475328460033473 Yes Department of Gynaecology and Obstetrics, The Second Clinical Medical College, China Three Gorges University, Yichang 443001, Hubei Province, China