Tanshinone IIA induces apoptosis of ovarian cancer cells in�vitro and in�vivo through attenuation of PI3K/AKT/JNK signaling pathways

Abstract

Ovarian cancer is one of the most common gynecological tumors and is the second most common cause of gynecological cancer-associated mortality worldwide. Tanshinone IIA (Tan-IIA) possesses anticancer activities through inducing the apoptosis of tumor cells. The purpose of the present study was to analyze the ability of Tan-IIA to induce apoptosis of human ovarian cancer cells <i>in vitro</i> and <i>in vivo</i>, and to examine the potential mechanism underlying its activity. Western blot analysis, immunohistochemistry and flow cytometry were used to analyze the therapeutic effects of Tan-IIA on ovarian cancer. It was demonstrated that Tan-IIA significantly inhibited the growth and aggressiveness of human ovarian cancer cells. Tan-IIA significantly increased the apoptosis of human ovarian cancer cells through cleavage activation of caspases-3, caspase-8 and caspases-9. In addition, Tan-IIA treatment decreased the expression of mitochondrial-protective B-cell lymphoma 2-like protein 2 (Bcl-w) and myeloid cell leukemia-1 long (Mcl-1L) in ovarian cancer cells. Tan-IIA also reduced the expression of phosphoinositide 3-kinase (PI3K), AKT and c-Jun N-terminal kinase (JNK) in human ovarian cancer cells. A specific PI3K inhibitor (LY294002) enhanced the Tan-IIA-inhibited expression of AKT and JNK. The overexpression of PI3K negated the Tan-IIA-inhibited expression of AKT and JNK, and eliminated the Tan-IIA-induced apoptosis of human ovarian cancer cells. Additionally, the <i>in vivo</i> assay showed that Tan-IIA treatment inhibited the growth of ovarian cancer through increasing the apoptosis of tumor cells. In conclusion, these findings suggested that the induction of apoptosis by Tan-IIA involves the PI3K/AKT/JNK signaling pathways in ovarian cancer.