MicroRNAs (miRNAs) are a class of naturally occurring, small, non-coding RNAs which play important roles in diverse biological processes and are acting as key regulators of tumorigenesis and chemotherapy resistance. In this study, a downregulation of miR-125b was observed in breast cancer cell lines, suggesting miR-125b is a tumor suppressor in breast cancer. Moreover, the miR-125b levels were significantly decreased in doxorubicin-resistant MCF-7 (MCF-7/DR) cells compared with MCF-7 cells. Transfection of miR-125b significantly enhanced the cytotoxicity of doxorubicin to MCF-7/DR cells. However, the overexpression of miR-125b did not influence the doxorubicin accumulation but downregulated the myeloid cell leukemia-1 (Mcl-1) levels, which may be the mechanism of apoptosis induction caused by doxorubicin combining with miR-125b in MCF-7/DR cells. Furthermore, luciferase reporter assay proved that Mcl-1 is the target of miR-125b. Importantly, we found that the sensitization of miR-125b to doxorubicin cytotoxicity is caspase-dependent in MCF-7/DR cells, which can be inhibited by zVAD-fmk. Finally, we indicated that the treatment of miR-125b plus doxorubicin leads to loss of mitochondrial membrane potential (MMP) and mitochondria outer membrane permeability (MOMP), which were interacted with the activation of caspases. Thus, this study revealed the role of miR-125b in doxorubicin resistance and therapy, which may provide novel approaches for the treatment of breast cancer.

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Context: Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is one of the most extensively used herbs for stroke and chronic debilitating conditions in East Asian countries. Ginsenosides (GS) are the main bioactive compounds for ginseng's efficacy, but the mechanisms have not been fully clarified. Objective: To investigate hepatoprotective effects of GS against ischemia/reperfusion (IR) injury in the experimental obstructive jaundice rats. Materials and methods: GS was fed to cholestatic rats with IR injury daily for 6 d at a dose of 1.10 g/kg. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined by colorimetric method. Apoptosis was measured quantitatively by the terminal transferase UTP nick end-labeling method. Protein expression of Bax and Bcl-2 was detected by immunohistochemistry. Results and discussion: After intervention of GS to cholestatic rats with IR injury, the levels of activating blood flow were significantly improved, and the levels of serum ALT were decreased 1.7-times, AST decreased 1.3-times, but SOD activities were increased 1.1-times compared with those of the model rats. It could also reverse histopathological changes and inhibit IR-induced apoptosis of hepatic tissues via decrease of Bax/Bcl-2 ratio (from 2.87 AE 0.57 to 1.65 AE 0.29). Oral administration of GS in a dosage of 26.4 g/kg did not lead to toxic effects in rats. Conclusion: GS attenuated the IR injury in the presence of cholestasis and could be considered for the clinical treatment of cholestasis.