Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju Special Self‑Governing Province 63243, Republic of Korea.
School of Biomaterials Science and Technology, College of Applied Life Sciences, Jeju National University, Jeju Special Self‑Governing Province 63243, Republic of Korea.
Oncol Rep. 2021 Mar;45(3):1133-1141. doi: 10.3892/or.2021.7924. Epub 2021 Jan 5.
Overcoming chemo‑ and radio‑resistance is a major challenge in pancreatic cancer treatment. Therefore, there is an urgent need to discover novel therapeutic approaches to avoid chemo‑ and radio‑resistance in pancreatic cancer. Catechol is a phytochemical found in some fruits and vegetables. A few studies have reported on the potential anticancer effects of pure catechol. The present study aimed to explore the chemo‑ and radio‑sensitizing effects of catechol in Panc‑1 human pancreatic cancer cells. The effects of catechol on Panc‑1 cell proliferation, clonogenic survival, invasion, and migration were assessed using MTT, cell migration, and Transwell invasion assays. The chemo‑ and radio‑sensitizing effects of catechol on Panc‑1 cells were evaluated via MTT assay and flow cytometry. Western blotting was conducted to analyze the expression of proteins involved in several mechanisms induced by catechol in Panc‑1 cells, including growth inhibition, apoptosis, suppression of epithelial‑mesenchymal transition (EMT), and chemo‑ and radio‑sensitizing activities. The results indicated that catechol inhibited proliferation, promoted apoptosis, and suppressed cell migration, invasion, and EMT in Panc‑1 cells in a dose‑dependent manner. Catechol treatment also induced the phosphorylation of AMP‑activated protein kinase (AMPK) with a concomitant reduction in the expression of Hippo signaling pathway components, including Yes‑associated protein, cysteine‑rich angiogenic inducer 61, and connective tissue growth factor. In addition, catechol enhanced the chemosensitivity of Panc‑1 cells to gemcitabine, a commonly used chemotherapy in pancreatic cancer treatment. A combination of catechol and radiation enhanced apoptosis and increased the expression of two radiation‑induced DNA damage markers, p‑ATM and p‑Chk2. Collectively, the present results demonstrated that catechol, a naturally occurring compound, could suppress the proliferation of pancreatic cancer cells, reduce the expression of EMT‑related proteins, and enhance the chemo‑ and radio‑sensitivity of Panc‑1 cells by targeting AMPK/Hippo signaling.
克服化疗和放疗耐药性是胰腺癌治疗的主要挑战。因此，迫切需要发现新的治疗方法来避免胰腺癌的化疗和放疗耐药性。儿茶酚是一种存在于某些水果和蔬菜中的植物化学物质。一些研究报道了纯儿茶酚的潜在抗癌作用。本研究旨在探讨儿茶酚对人胰腺癌细胞 Panc-1 的化疗和放疗增敏作用。采用 MTT、细胞迁移和 Transwell 侵袭实验评估儿茶酚对 Panc-1 细胞增殖、克隆存活、侵袭和迁移的影响。通过 MTT 法和流式细胞术评估儿茶酚对 Panc-1 细胞的化疗和放疗增敏作用。Western blot 分析儿茶酚在 Panc-1 细胞中诱导的几种机制相关蛋白的表达，包括生长抑制、凋亡、上皮间质转化（EMT）抑制和化疗放疗增敏活性。结果表明，儿茶酚呈剂量依赖性抑制 Panc-1 细胞增殖，促进凋亡，抑制细胞迁移、侵袭和 EMT。儿茶酚处理还诱导 AMP 激活蛋白激酶（AMPK）磷酸化，同时降低 Hippo 信号通路组件的表达，包括 Yes 相关蛋白、富含半胱氨酸的血管生成诱导因子 61 和结缔组织生长因子。此外，儿茶酚增强了 Panc-1 细胞对吉西他滨的化疗敏感性，吉西他滨是一种常用于胰腺癌治疗的化疗药物。儿茶酚与放疗联合增强了凋亡，并增加了两种放射诱导的 DNA 损伤标志物 p-ATM 和 p-Chk2 的表达。总之，本研究结果表明，儿茶酚作为一种天然化合物，可通过靶向 AMPK/Hippo 信号抑制胰腺癌细胞增殖，降低 EMT 相关蛋白的表达，并增强 Panc-1 细胞的化疗和放疗敏感性。
