SK-HEP1 세포에서 Actin Cytoskeleton과 NF-κB 신호 전달을 통한 Gambogic acid의 암전이 억제효과

Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with the highly metastatic potential. Therefore, the strategy to eradicate HCC metastasis is a critical target for effective therapies of HCC. Gambogic acid (GA) is a natural compound obtained from Garcinia hanburyi in Southeast Asia. GA has been reported for potential of anti-cancer activity in several cancer cell lines. However, anti-metastatic mechanisms of GA are still unclear, particularly on HCC. In this study, we focused on the influence of GA on migration and invasion of SK-HEP1 cells. The results indicated that GA at over 0.6 μM significantly reduced cell proliferation of SK-HEP1 cells, but did not affect cell proliferation of non-cancerous HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. Results of western blot analysis and immunofluorescence revealed that GA down-regulated the expression of integrin β1/rho family GTPases signaling pathway. Furthermore, F-actin staining showed that GA suppressed actin rearrangement related to cell cytoskeleton and migration. In addition, GA could decrease NF-κB-mediated MMP-2 and -9 expressions involved in cancer invasion. Taken together, our results suggest that GA could be used as a candidate for the anti-metastatic drug of HCC.