胰腺导管腺癌（PDAC）仍然是最具破坏性的疾病之一；其预后相当差，可能在接下来的10年内成为第二致命的恶性肿瘤。PDAC常见化疗耐药，因此，有必要开发有效的替代药物。近年来，传统民间药物及其提取物在癌症治疗中显示出巨大潜力。葫芦瓜的种子是亚洲传统药物。因其镇痛效果和减轻肿胀的能力，常用作辅助治疗腹部肿瘤。葫芦瓜酮类化合物是葫芦瓜的丰富提取物。在这里，我们发现葫芦瓜酮C（CuC）作为葫芦瓜酮家族的成员，具有明显的抗PDAC治疗特性。CuC以时间和剂量依赖的方式降低了PDAC细胞的存活率，并抑制了细胞的增殖。进一步研究表明，CuC通过抑制上皮-间质转化（EMT）来抑制细胞迁移和侵袭。此外，CuC诱导了G2/M期阻滞，并激活了凋亡通路。转录组学和生物信息学分析显示，CuC抑制了cGMP-PKG-VASP轴，增加了cGMP含量以恢复肿瘤特征。通过动物实验验证了CuC在体内的抗肿瘤活性，且未观察到明显的副作用。总而言之，我们的研究表明了一种值得进一步开发的PDAC治疗候选化合物。 版权©2023 Elsevier Inc.发表。

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating diseases; it has a considerably poor prognosis and may become the second most lethal malignancy in the next 10 years. Chemotherapeutic resistance is common in PDAC; thus, it is necessary to exploit effective alternative drugs. In recent years, traditional folk medicines and their extracts have shown great potential in cancer treatment. The seed of Lagenaria siceraria (Molina) Standl. is a traditional medicine in Asia. Because of its analgesic effects and ability to reduce swelling, it is often used as an adjuvant treatment for abdominal tumors. Cucurbitacin compounds are extracts abundant in Lagenaria siceraria (Molina) Standl. Here, we found that cucurbitacin C (CuC), a member of the cucurbitacin family, has apparent anti-PDAC therapeutic properties. CuC decreased the viability and suppressed the proliferation of PDAC cells in a time- and dose-dependent manner. Further studies revealed that CuC inhibited cell migration and invasion by inhibiting epithelial-mesenchymal transition (EMT). In addition, G2/M arrest was induced, and the apoptotic pathway was activated. Transcriptomic and bioinformatic analyses showed that CuC inhibited the cGMP-PKG-VASP axis, increasing the content of cGMP to restore tumor characteristics. The antitumor activity of CuC in vivo was verified through animal experiments, and no obvious side effects were observed. Overall, our study indicates a candidate therapeutic compound for PDAC that is worthy of further development.Copyright © 2023. Published by Elsevier Inc.