School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan; Department of Otolaryngology, St. Martin De Porres Hospital, Chiayi, Taiwan.
Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Oral Oncol. 2024 Dec;159:107038. doi: 10.1016/j.oraloncology.2024.107038. Epub 2024 Sep 15.
Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism.
Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors.
In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells.
Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.
转移性疾病是鼻咽癌（NPC）患者治疗失败的主要问题，通常与高死亡率有关。L48H37 是姜黄素的一种合成类似物，其生物利用度高于其母体化合物，具有多种抗肿瘤特性。本研究旨在探讨 L48H37 对 NPC 癌细胞的抗转移作用及其潜在机制。
采用 MTT 法评估细胞活力。通过免疫印迹和特定的激酶抑制剂阐明信号通路的调节。
在这项研究中，我们表明 L48H37 抑制了 TPA 刺激的 NPC 细胞系的侵袭和迁移能力，并且几乎没有产生细胞毒性反应。L48H37 的这种抗癌作用伴随着基质金属蛋白酶-9（MMP-9）表达水平和酶活性的降低，MMP-9 是转移过程的关键介质。此外，L48H37 干扰了 TPA 诱导的 JNK 激活，并且 L48H37 与 JNK 拮抗剂联合治疗对抑制 TPA 刺激的 MMP-9 活性和 NPC 细胞迁移事件表现出协同作用。
我们的结果表明，L48H37 通过损害 MMP-9 的功能和丰度来抑制 NPC 细胞的侵袭潜力，强调了使用姜黄素或其有效类似物进行可能的补充治疗来管理 NPC 传播的潜力。
