PAK4-PROTAC targeted degradation drug enhances immune cell-induced apoptosis in renal cell carcinoma
10.3969/j.issn.1009-8291.2025.06.013
- VernacularTitle:PAK4-PROTAC靶向降解药物PpD促进免疫细胞杀伤肾癌细胞的研究
- Author:
Chen YAO
1
;
Bohan MA
1
;
Xiaojing BAI
2
;
Shan XU
1
Author Information
1. Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061; Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China
2. Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061
- Publication Type:Journal Article
- Keywords:
renal cancer;
p21 activated kinases 4;
PAK4-PROTAC targeted degradation drug;
co-culture;
immunotherapy
- From:
Journal of Modern Urology
2025;30(6):527-532
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the potential application of PAK4-PROTAC targeted degradation drug (PpD) in renal cancer immunotherapy. Methods: TIMER 2.0 and TISIDB databases were used to analyze the relationship among PAK4 expression, tumor purity and abundance of immune cell infiltration in renal tumor microenvironment (TEM).Renal cancer cell lines OS-RC-2, 786-O and ACHN were treated with 0, 125 and 250 nmol/L PpD, and the effects of Jurkat cell co-culture on the results were investigated.The cell apoptosis was detected with flow cytometry, and the expression of programmed cell death 1 ligand 1 (PD-L1) in renal cancer cells was detected with immunoblotting. Results: The high expression of PAK4 was positively related to immune purity, and inhibited the abundance of immune killer cells in TEM, such as CD8 T cells, CD4 T cells, natural killer cells and dendritic cells.With 250 nmol/L PpD treatment, there were 21.02% apoptotic cells in OS-RC-2, 29.67% apoptotic cells in 786-O, and 15.39% apoptotic cells in ACHN, respectively.However, with the same concentration of 250 nmol/L PpD treatment, cell apoptotic rate was sharply increased to 70.13% in OS-RC-2/Jurkat, 70.68% in 780-O/Jurkat, and 60.27% in ACHN/Jurkat co-culture models, respectively. Conclusion: PpD can promote apoptosis of renal cancer cells by reducing the expression of PAK4 protein, and enhance the killing effects of immune cells on tumor cells.
