PDF(Pubmed)
Abstract：
The limited success of current targeted therapies for pancreatic cancer underscores an urgent demand for novel treatment modalities. The challenge in mitigating this malignancy can be attributed to the digestive organ expansion factor (DEF), a pivotal yet underexplored factor in pancreatic tumorigenesis. The study uses a blend of in vitro and in vivo approaches, complemented by the theoretical analyses, to propose DEF as a promising anti-tumor target. Analysis of clinical samples reveals that high expression of DEF is correlated with diminished survival in pancreatic cancer patients. Crucially, the depletion of DEF significantly impedes tumor growth. The study further discovers that DEF binds to p65, shielding it from degradation mediated by the ubiquitin-proteasome pathway in cancer cells. Based on these findings and computational approaches, the study formulates a DEF-mimicking peptide, peptide-031, designed to disrupt the DEF-p65 interaction. The effectiveness of peptide-031 in inhibiting tumor proliferation has been demonstrated both in vitro and in vivo. This study unveils the oncogenic role of DEF while highlighting its prognostic value and therapeutic potential in pancreatic cancer. In addition, peptide-031 is a promising therapeutic agent with potent anti-tumor effects.
摘要：
目前胰腺癌靶向治疗的有限成功强调了对新治疗方式的迫切需求。减轻这种恶性肿瘤的挑战可以归因于消化器官扩张因子（DEF）。胰腺肿瘤发生中一个关键但未被开发的因子。这项研究使用了体外和体内方法的混合，在理论分析的补充下，提出DEF作为一个有希望的抗肿瘤靶点。临床样品的分析揭示了DEF的高表达与胰腺癌患者的存活率降低相关。至关重要的是，DEF的消耗显著阻碍肿瘤生长。该研究进一步发现DEF与p65结合，使其免受癌细胞中泛素-蛋白酶体途径介导的降解。基于这些发现和计算方法，这项研究制定了一种模拟DEF的肽，肽-031，旨在破坏DEF-p65相互作用。已经在体外和体内证明了肽-031抑制肿瘤增殖的有效性。这项研究揭示了DEF的致癌作用，同时强调了其在胰腺癌中的预后价值和治疗潜力。此外,肽-031是具有有效抗肿瘤作用的有前途的治疗剂。
