Kim Dong Hwi, Yong Hyo Jeong, Mander Sunam, Nguyen Huong Thi, Nguyen Lan Phuong, Park Hee-Kyung, Cha Hyo Kyeong, Kim Won-Ki, Hwang Jong-Ik
Department of Biomedical Science, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Department of Neuroscience, Korea University College of Medicine, Seoul 02841, Republic of Korea.
Biomol Ther (Seoul). 2021 May 1;29(3):331-341. doi: 10.4062/biomolther.2020.200.
Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.
肝癌是一种常见肿瘤，目前是全球癌症相关死亡的第二大主要原因。肝癌与炎症高度相关，因为超过90%的肝癌发生在肝脏炎症背景下，如乙型肝炎病毒和丙型肝炎病毒感染。尽管肝癌治疗方式有显著改善，但由于目前药物疗法在抗转移活性方面疗效有限，患者预后并不理想。因此，开发具有抗转移活性的新型有效抗癌药物对肝癌治疗至关重要。在本研究中，研究了具有抗炎活性的马鞭草烯酮衍生物SP-8356对肝癌细胞生长和迁移的影响。我们的研究结果表明，SP-8356通过诱导凋亡以及抑制肝癌细胞的迁移和侵袭能力来抑制肝癌细胞增殖。功能研究显示，SP-8356抑制与细胞增殖和转移相关的丝裂原活化蛋白激酶和核因子-κB信号通路，导致转移相关基因下调。此外，使用原位肝癌模型，用SP-8356治疗后肿瘤生长显著降低。因此，本研究表明SP-8356可能是一种具有多模式调节作用的肝癌治疗潜在药物。
