Effect of berbamine on invasion and metastasis of human liver cancer SMMC-7721 cells and its possible mechanism.

Berbamine is a bisbenzylisoquinoline alkaloid extracted from Berberis poiretii of Berberis of Berberidaceae. It has been reported that it can significantly inhibit the proliferation of a variety of malignant tumor cells, including liver cancer. However, the effect of berbamine on the invasion and metastasis of liver cancer has not been reported. The present study demonstrated that berbamine inhibited the migration and invasion of SMMC-7721 cells in a concentration-dependent manner and obviously increased the gap junction function and the expression of Cx32 in SMMC-7721 cells compared with control group. However, after silencing Cx32, berbamine had no significant effect on cell invasion and metastasis. Before silencing Cx32, the expression of PI3K and P-AKT were decreased after berbamine treated on SMMC-7721 cells for 24 h. After silencing Cx32, the expression of PI3K and P-AKT were increased in SMMC-7721 cells. The expression of PI3K and P-AKT had no significant effect after berbamine treated on SMMC-7721 cells for 24 h with silencing Cx32. In conclusion, the results of the present study suggest that berbamine could inhibit the SMMC-7721 cell migration and invasion, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway by enhancing the expression of Cx32.

DNMT1 promotes cell proliferation via methylating hMLH1 and hMSH2 promoters in EGFR-mutated non-small cell lung cancer.

Aberrant DNA methylation is a common form of epigenetic alterations and it has been proved to be closely related to many cancers, while its role in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is not clear. This study focuses on the role of DNA methyltransferase 1 (DNMT1) in EGFR-mutated NSCLC pathogenesis. First, the expression of DNMT1 was up-regulated, while the expressions of human mutL homolog 1(hMLH1) and human mutS homolog 2 (hMSH2) were down-regulated in EGFR-mutated NSCLC patients and cell line HCC827. The results of the correlation analysis showed that DNMT1 expression was inversely correlated with the expressions of hMLH1 and hMSH2. Then, we found that DNMT1 enhanced the promoter methylation levels of hMLH1 and hMSH2, thus suppressing their expressions. DNMT1 knockdown inhibited the proliferation of HCC827 cells, while both hMLH1 knockdown and hMSH2 knockdown could eliminate its inhibitory effect on cell proliferation. In xenograft mouse models, lentiviral vector-sh-DNMT1 could significantly reduce tumor volumes, confirmed that DNMT1 inhibited tumor cell proliferation in vivo. In conclusion, DNMT1 suppressed the expressions of hMLH1 and hMSH2 via elevating their promoter methylation, thus promoting cell proliferation in EGFR-mutated NSCLC.