Park Geumi, Song Na-Young, Kim Do-Hee, Lee Su-Jun, Chun Kyung-Soo
College of Pharmacy, Keimyung University, Daegu 42601, Republic of Korea.
College of Dentistry, Younsei University, Seoul 03722, Republic of Korea.
Biomol Ther (Seoul). 2021 Jan 1;29(1):64-72. doi: 10.4062/biomolther.2020.048.
Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of , has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E (PGE) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprostinduced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.
肾细胞癌（RCC）容易转移至其他器官，且通常对传统化疗耐药。百里醌（TQ）是一种从黑种草种子中提取的植物化学物质，已被证明可抑制多种癌症的迁移和转移。在本研究中，我们评估了TQ对人RCC Caki-1细胞迁移活性的影响。我们发现，用TQ处理可降低Caki-1细胞中基质金属蛋白酶-9（MMP-9）的蛋白水解活性。TQ显著抑制前列腺素E（PGE）的产生、其EP2受体的表达以及Akt和p38的激活，Akt和p38是MMP-9众所周知的上游信号蛋白。此外，用PGE激动剂布他前列素处理也可诱导Caki-1细胞中的MMP-9活性以及迁移/侵袭。而且，PI3K/Akt和p38的药理抑制剂显著减弱了布他前列素诱导的Caki-1细胞迁移和侵袭，这意味着PI3K/Akt和p38的激活是PGE-EP2轴与MMP-9依赖性迁移和侵袭之间的桥梁。综上所述，这些数据表明TQ是一种有前景的抗转移药物，可用于治疗晚期和转移性RCC。
