잠시만 기다려 주세요. 로딩중입니다.

Thymoquinone Suppresses Migration of Human Renal Carcinoma Caki-1 Cells through Inhibition of the PGE2-Mediated Activation of the EP2 Receptor Pathway

Biomolecules & Therapeutics 2021년 29권 1호 p.64 ~ 72
박금이, 송나영, 김도희, 이수준, 천경수,
소속 상세정보
박금이 ( Park Geum-I ) - Keimyung University College of Pharmacy
송나영 ( Song Na-Young ) - Yonsei University College of Dentistry
김도희 ( Kim Do-Hee ) - Kyonggi University College of Convergence and Integrated Science Department of Chemistry
이수준 ( Lee Su-Jun ) - Inje University College of Medicine Department of Pharmacology
천경수 ( Chun Kyung-Soo ) - Keimyung University College of Pharmacy

Abstract


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 Nigella sativa, 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 E2 (PGE2) 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 PGE2 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 PGE2-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.

키워드

Thymoquinone; Renal cell carcinoma (RCC); Prostaglandin E2 (PGE2); EP2 receptor; MMP-9

원문 및 링크아웃 정보

등재저널 정보