Matrine inhibits ovarian cancer cell viability and promotes apoptosis by regulating the ERK/JNK signaling pathway via p38MAPK

Abstract

Ovarian cancer displays the highest mortality rate among all types of gynecological cancer worldwide. The survival of patients with ovarian cancer remains poor due to poor responses to anticancer treatments. The present study aimed to investigate the therapeutic effects and potential mech- anism underlying matrine in ovarian cancer tissues, ovarian cancer cells and a CAOV-3-derived tumor-bearing mouse model. MTT, migration, invasion, flow cytometry, immunoflu- orescence and immunohistochemistry assays were performed to assess the inhibitory effects of matrine on ovarian cancer. A xenograft ovarian cancer mouse model was established and treated with matrine or PBS. The results demonstrated that compared with the control group, matrine significantly induced ovarian cancer cell apoptosis by upregulating caspase-8 and Fas cell surface death receptor (Fas) expression levels, and downregulating Bcl-2 and Bcl-xl expression levels. Moreover, compared with the control group, matrine significantly inhib- ited ovarian cancer cell viability, migration and invasion by downregulating metastasis associated protein-1, fibronectin, angiotensin II type 2 receptor–interacting protein 3a and H high mobility group AT-hook 2 expression levels. Compared with the control group, matrine significantly increased p38MAPK, phosphorylated (p)ERK/ERK and pJNK/JNK expression levels in ovarian cancer cells. p38MAPK knockdown signifi- cantly downregulated p38MAPK, pERK/ERK and pJNK/JNK expression levels compared with the control group, which significantly promoted ovarian cancer cell viability, migration and invasion. In vivo experiments demonstrated that compared with the control group, matrine significantly suppressed tumor growth by markedly upregulating p38MAPK, ERK and JNK expression levels. The immunohistochemistry results demon- strated that caspase-8 and Fas expression levels were notably increased, whereas Bcl-2 and Bcl-xl expression levels were obviously decreased in matrine-treated tumors compared with PBS-treated tumors. In conclusion, the present study demon- strated that matrine inhibited ovarian cancer cell viability, migration and invasion, but induced cell apoptosis, suggesting that matrine may serve as a promising anticancer agent for the treatment of ovarian cancer.