Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A

摘要

Context: Portulacerebroside A (PCA) is a novel cerebroside compound isolated from Portulaca oleracea L. (Portulacaceae), an edible and medicinal plant distributed in the temperate and tropical zones worldwide.Objective: This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion.Materials and methods: After the cells were treated with PCA (2.5, 5, and 10?μg/ml) for 6, 12, 24, or 48?h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells.Results: The adhesion rate of the cells was suppressed at 0.5?h (79.4?±?1.0, 68.7?±?1.3, and 58.1?±?1.3%, versus 100?±?1.5% in the control), 1?h (78.2?±?1.2, 70.9?±?1.6, and 55.4?±?1.9%, versus 100?±?1.2% in the control), and 1.5?h (71.6?±?1.1, 62.3?±?0.9, and 50.4?±?0.9%, versus 100?±?1.1% in the control). The 24?h invasion ability was decreased (356.6?±?11.2, 204.0?±?17.6, and 113.0?±?9.5%, versus 443.6?±?15.4% in the control). The migration capability was also restrained by PCA for 24?h (324.8?±?25.4, 250.4?±?21.0, and 126.3?±?10.1, versus 381.6?±?30.6 in the control) and 48?h (470.3?±?34.3, 404.0?±?19.7, and 201.0?±?15.4, versus 752.0?±?63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9.Conclusion: PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.