Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Phytother Res. 2021 Apr;35(4):2200-2210. doi: 10.1002/ptr.6971. Epub 2020 Nov 30.
Pancreatic ductal adenocarcinoma (PDAC) is severe malignant tumor in human, the outcomes of PDAC is extremely poor. Here, we evaluated the potential anti-tumor activity of chlorogenic Acid (CA) in PDAC. Here, we found CA was effective to suppress PDAC cell growth in vitro and in vivo. Importantly, we found overall oxygen consumption rate was significantly decreased in CA dose-dependent manner. We also found glycolysis reverse was decreased in CA-treated cells, while basal glycolysis and glycolytic capacity were not significantly changed. Mechanistically, we demonstrated TFR1 could be a novel downstream target of CA, which is essential for PDAC cell growth and cellular bioenergetics maintenance. Furthermore, we validated that CA-reduced c-Myc resulted to down-regulation of TFR1, which contributes to mitochondrial respiration dysfunction and cell growth delay. Together, this study indicates that CA suppresses PDAC cell growth through targeting c-Myc-TFR1 axis and suggests CA could be considered as a promising compound for PDAC treatment.
胰腺导管腺癌（PDAC）是人类严重的恶性肿瘤，PDAC 的预后极差。在这里，我们评估了绿原酸（CA）在 PDAC 中的潜在抗肿瘤活性。在这里，我们发现 CA 在体外和体内均能有效抑制 PDAC 细胞生长。重要的是，我们发现 CA 呈剂量依赖性地显著降低总耗氧量。我们还发现 CA 处理的细胞中糖酵解逆转减少，而基础糖酵解和糖酵解能力没有明显变化。在机制上，我们证明 TFR1 可能是 CA 的一个新的下游靶点，对于 PDAC 细胞生长和细胞能量代谢维持是必需的。此外，我们验证了 CA 降低 c-Myc 导致 TFR1 下调，这有助于线粒体呼吸功能障碍和细胞生长延迟。总之，这项研究表明，CA 通过靶向 c-Myc-TFR1 轴抑制 PDAC 细胞生长，并提示 CA 可被考虑作为 PDAC 治疗的一种有前途的化合物。
