Wei Zhao1, Juan Li2, Ping Li2, Fei Guo1, Pengfei Gao1, Junjie Zhang1, Zechen Yan3, Lei Wang1, Da Zhang1, Pan Qin1, Guoqiang Zhao4, Jiaxiang Wang5. 1. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Erqi District, Zhengzhou, 450000, Henan, China. 2. Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Erqi District, Zhengzhou, 450000, Henan, China. 3. Department of Urinary Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Erqi District, Zhengzhou, 450000, Henan, China. 4. Department of Microbiology and Immunology, Basic Medical College, Zhengzhou University, No. 100 Kexuedadao Road, Zhongyuan District, Zhengzhou, 450001, Henan, China. 5. Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Erqi District, Zhengzhou, 450000, Henan, China. jiaxiangwangzzu@126.com.
Abstract
BACKGROUND: Our previous study identified a Wilms tumor-suppressing peptide (WTSP) that was upregulated in healthy children, but downregulated in children with Wilms tumor (WT). This study aimed to investigate the effect of WTSP on WT growth in vivo and in vitro. METHODS: WTSP was synthesized by solid-phase synthesis of FOMC-protected amino acids. Cell growth curve, cytotoxicity, and apoptosis of WTSP-treated human WT cell line (SK-NEP-1) were determined by cell count, Cell Counting Kit-8 assay, and flow cytometry. The expression of key proteins of four WT-associated signaling pathways was determined by real-time PCR and western blotting. The WT xenograft mouse model was established by the armpit injection of SK-NEP-1 cells. The TUNEL assay was used to detect apoptosis in mouse tumor cells. RESULTS: WTSP inhibited the proliferation of SK-NEP-1 cells in a dose- and time-dependent manner, and it arrested SK-NEP-1 cells in G2/M phase. WTSP-treated cells exhibited a low expression of PCNA and Bcl-2 and high expression of Bax. The expression of β-catenin was markedly changed after WTSP treatment. WTSP-treated mice had significantly smaller tumors than untreated mice. CONCLUSION: Our findings indicated an anti-tumor effect of WTSP, which is correlated with Wnt/β-catenin pathway. This newly identified peptide may exert a therapeutic effect of WT in the future.
BACKGROUND: Our previous study identified a Wilms tumor-suppressing peptide (WTSP) that was upregulated in healthy children, but downregulated in children with Wilms tumor (WT). This study aimed to investigate the effect of WTSP on WT growth in vivo and in vitro. METHODS: WTSP was synthesized by solid-phase synthesis of FOMC-protected amino acids. Cell growth curve, cytotoxicity, and apoptosis of WTSP-treated human WT cell line (SK-NEP-1) were determined by cell count, Cell Counting Kit-8 assay, and flow cytometry. The expression of key proteins of four WT-associated signaling pathways was determined by real-time PCR and western blotting. The WT xenograft mouse model was established by the armpit injection of SK-NEP-1 cells. The TUNEL assay was used to detect apoptosis in mousetumor cells. RESULTS: WTSP inhibited the proliferation of SK-NEP-1 cells in a dose- and time-dependent manner, and it arrested SK-NEP-1 cells in G2/M phase. WTSP-treated cells exhibited a low expression of PCNA and Bcl-2 and high expression of Bax. The expression of β-catenin was markedly changed after WTSP treatment. WTSP-treated mice had significantly smaller tumors than untreated mice. CONCLUSION: Our findings indicated an anti-tumor effect of WTSP, which is correlated with Wnt/β-catenin pathway. This newly identified peptide may exert a therapeutic effect of WT in the future.
Entities:
Keywords:
Tumor-suppressing peptide; Wilms tumor; m/z 6455.5 Da; β-Catenin
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