Breast cancer is the second most common cause of cancer-associated mortality among women worldwide, and triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Berbamine (BBM) is a traditional Chinese medicine used for the treatment of leukopenia without any obvious side effects. Recent reports found that BBM has anti-cancer effects. The present study aimed to investigate the effects of BBM on TNBC cell lines and the underlying molecular mechanism. MDA-MB-231 cells and MCF-7 cells, two TNBC cell lines, were treated with various concentrations of BBM. A series of bioassays including MTT, colony formation, EdU staining, apoptosis, trypan blue dye, wound healing, transwell, ELISA and western blotting assays were performed. The results showed that BBM significantly inhibited cell proliferation of MDA-MB-231 cells (P<0.05; IC 50 =22.72 µM) and MCF-7 cells (P<0.05; IC 50 =20.92 µM). BBM (20 µM) decreased the apoptosis ratio (percentage of absorbance compared with the control group) by 28.4±3.3% (P<0.05) in MDA-MB-231 cells, and 62.4±24.6% (P<0.05) in MCF-7 cells. In addition, BBM inhibited cell migration and invasion of TNBC cells. Furthermore, the expression levels of PI3K, phosphorylated-Akt/Akt, COX-2, LOX, MDM2 and mTOR were downregulated by BBM, and the expression of p53 was upregulated by BBM. These results indicated that BBM may suppress the development of TNBC via regulation of the PI3K/Akt/MDM2/p53 and PI3K/Akt/mTOR signal pathways. Therefore, BBM might be used as a drug candidate for the treatment of TNBC in the future.

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.

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.

For a long time, people have been eager to realize continuous real-time online monitoring of biological compounds. Fortunately, in vivo electrochemical biosensor technology has greatly promoted the development of biological compound detection.