Hedyotis diffusa plus Scutellaria barbata Induce Bladder Cancer Cell Apoptosis by Inhibiting Akt Signaling Pathway through Downregulating miR-155 Expression

Traditional Chinese medicine is increasingly used to treat cancer. Our clinical experiences identify Hedyotis diffusa plus Scutellaria barbata as the most common herb-pair (couplet medicinal) used for the core treatment of bladder cancer. This study aims to investigate the antitumor effect of the herb-pair in bladder cancer cells. The results show that Hedyotis diffusa plus Scutellaria barbata inhibited bladder cancer cell growth and clone formation in a dose-dependent and time-dependent manner. It also induced cell apoptosis through decreasing Akt activation and reducing the expression of antiapoptotic proteins Bcl-2 and Mcl-1. Further experiments showed that miR-155 was reduced by the herb-pair and miRNA-155 inhibitor induced cell apoptosis and suppressed Akt activation. Overexpression of miR-155 reversed herb-pair induced cell apoptosis through activating Akt pathway in both bladder cancer cell lines. The findings reveal that Hedyotis diffusa plus Scutellaria barbata reduce Akt activation through reducing miR-155 expression, resulting in cell apoptosis. It demonstrated the potential mechanism of Hedyotis diffusa plus Scutellaria barbata for the core treatment of bladder cancer.