Inhibition of Wilms' Tumor Proliferation and Invasion by Blocking TGF-β Receptor I in the TGF-β/Smad Signaling Pathway

Wilms' tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor beta (TGF-beta) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-beta contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-beta signaling pathway was involved in WT and whether blocking T beta RI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-beta 1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a T beta RI kinase inhibitor or PBS. High protein levels of TGF-beta 1 and P-samd2/3 were associated with clinical stage and metastasis or invasion. T beta RI inhibition effectively suppressed WT proliferation and migration and promoted apoptosis in the human WT cell line G401, consequently decreasing EMT protein expression. In addition, the T beta RI kinase inhibitor significantly impaired the subcutaneous growth of WT. It is worth noting that treatment with the T beta RI kinase inhibitor did not cause liver and kidney injury. Our results indicate that the TGF-beta/Smad signaling pathway plays a crucial role in WT progression. Blocking the T beta RI receptor may be a novel strategy to treat and prevent WT.