期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 40, 期 7, 页码 3082-3097出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1845241
关键词
Biomimetic strategy; beta-catenin/LRH-1 complex; pancreas cancer; peptide inhibitor; protein-protein interaction
资金
- Kermanshah University of Medical Sciences [97468]
Recent studies have suggested that inhibiting the formation of the beta-catenin/LRH-1 complex may be a potential strategy for inhibiting the progression of pancreatic cancer cells. In this study, a biomimetic approach was used to design an affinity peptide that showed inhibitory effects on the Wnt signaling pathway and induced apoptosis in pancreatic cancer cells. The peptide also demonstrated inhibitory effects on the stemness feature of the cells.
Poor prognosis, rapid progression and the lack of an effective treatment make pancreatic cancer one of the most lethal malignancies. Recent studies point to a role for liver receptor homolog-1 (LRH-1) in pathogenesis of pancreatic cancer and suggest prevention of the beta-catenin/LRH-1 complex formation as a potential strategy for inhibition of the pancreas cancer cells progression. In the current investigation, we have followed a biomimetic strategy and designed an affinity peptide with sequence DEMEEPQQTE to inhibit formation of the beta-catenin/LRH-1 complex. Quantitative real-time PCR experiments on the AsPC-1 pancreatic metastatic cells showed that the peptide has an inhibitory effect on the Wnt signaling proliferation line by reducing the expression levels of the CCND1, CCNE1, and MYC genes. Furthermore, the increased expression level of BAX gene showed that AsPC-1 cells were directed to the apoptosis pathway. At last, POU5F1, KLF4, and CD44 gene expression levels suggested that the peptide has an inhibitory effect on the stemness feature of the AsPC-1 cells. Here, we introduced a novel peptide inhibitor targeting an important protein-protein interaction, the beta-catenin/LRH-1 complex, which may provide highly promising starting points for subsequent drug design. Communicated by Ramaswamy H. Sarma
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