ZSTK474 Targeting PIK3R3 Inhibits the Wilms' Tumor through G0 / G1 Phase Arrest

Purpose: Wilms' tumor (WT) is children's most common primary kidney malignancy. The prognosis of patients with anaplastic and recurrent nephroblastoma is still poor. Therefore, searching for a new potential medicinal agent for WT is urgent. Methods We used one-way Cox regression and Kaplan-Meier analysis to identify differentially expressed and prognostic-related genes (p < 0.05) based on the nephroblastoma dataset TARGET-WT in the TCGA database. We predicted ZSTK474, a PI3K inhibitor, as a potential therapeutic agent for WT by querying the Connectivity Map (CMap) database for prognosis-related genes. The inhibitory effect of ZSTK474 on WT was investigated by in vivo and in vitro experiments, and its inhibitory mechanism was explored. Results In vivo, ZSTK474 inhibited the growth of nephroblastoma in a dose-dependent manner, and no significant toxic side effects were observed. Western blot and immunofluorescence