Stellettin B Suppresses Human Hepatocellular Cacinoma Cell Migration and Invasion through MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways

Stellettin B, isolated by wild-type sponge Stelletta sp. from the ocean, exhibited potent antiprolifertive activities on various tumor cells. In this study, we use demonstrated the stellettin B inhibited the migration and invasion of the hepatocellular carcinoma cell HA22T/VGH. We found that the stellettin B inhibited the invasion and migration of hepatocellular carcinoma cells in a dose-dependent manner. The results of zymography assay showed that stellettin B suppressed the activities of matrix metalloproteinase MMP-9 and MMP-2. Moreover, protein levels of MMP-9, MMP-2, and urokinase-type plasminogen activator (uPA) were reduced by stellettinB in a dose-dependent manner. Stellettin B also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), phosphatidylinositol 3-kinase (PI3K) and Akt. Taken together, these results demonstrated that stellettin B could inhibit hepatocellular carcinoma cell migration and invasion and alter HA22T/VGH cell metastasis by reduction of uPA, MMP-2 and MMP-9 expression through the suppression of MAPKs and FAK/PI3K/AKT/mTOR signaling pathway. These findings suggest that stellettin B merits further evaluation as a chemotherapeutic agent for human hepatocellular carcinoma.

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