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

BACKGROUND

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.

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.

CONCLUSIONS

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.