Abstract
BACKGROUND: In Chinese herbal medicine, Tanshinone IIA (Tan-IIA) is one of the main compounds extracted from Salvia miltiorrhiza Bunge. Tan-IIA has been demonstrated to inhibit the growth of various tumors. However, the detailed molecular and cellular mechanisms of the antitumor effect of Tan-IIA have yet to be fully illuminated. METHODS: A2780 and ID-8 were treated with 0, 1.2, 2.4, 4.8, or 9.6 µg/mL Tan-IIA for 24 hours. Cell counting Kit-8 assay and EdU staining were used to evaluate cell proliferation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry were performed to analyze apoptosis. Western blot was carried out to determine the protein levels. Flow cytometry was used for cell cycle analysis. The levels of mRNA expression were analyzed by real-time polymerase chain reaction. The anti-tumor effect of Tan-IIA was observed in a tumor-bearing mouse model. RESULTS: Tan-IIA inhibited the proliferation of ovarian cancer cells in a dose-dependent manner by inducing G2/M phase arrest. It also down-regulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax) in ovarian cancer cells to induce apoptosis, and suppressed cell migration by inhibiting focal adhesion kinase phosphorylation. Tan-IIA significantly reduced vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX2) mRNA expression in ovarian cancer cells. In vivo, Tan-IIA significantly inhibited tumor growth by inducing apoptosis and promoting anti-angiogenesis. CONCLUSIONS: The results of this study shed light on the molecular and cellular mechanisms for the antitumor effect of Tan-IIA.