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Effective chemotherapeutic strategies for uterine sarcoma are lacking; existing therapies achieve poor response rates. Previous studies have identified the prostaglandin 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) as a potential anticancer treatment; however, its effectiveness in uterine sarcoma has not been examined. Furthermore, the molecular mechanisms underlying the cytotoxic mechanism of 15d-PGJ2 remain unclear. Here, we evaluated the effects of 15d-PGJ2 alone and in combination with the tyrosine kinas inhibitor (TKI) dasatinib in uterine sarcoma cell lines (MES-SA, MES-SA/DX5 and SKN). 15d-PGJ2 inhibited cell growth and increased apoptosis. Western blotting demonstrated that 15d-PGJ2 treatment increased MEK and ERK phosphorylation, and decreased levels of phosphorylated AKT. Dasatinib in combination with 15d-PGJ2 significantly reduced cell proliferation compared with 15d-PGJ2 alone, and repressed both the AKT and MAPK pathways. The cell growth inhibition rate in the PGJ2 was 21.5±12.0, 35.3±5.4 and 28.3±4.2%, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the cell growth inhibition rate in the combination therapy was significantly higher compared with 15d-PGJ2 alone (MES-SA; 64.2±0.8, MES-SA/DX5;23.9±8.2 and SKN; 41.4±17.6%). The PGJ2 IC50 determined by MTT assay was 27.41,10.46 and 17.38 µmol/l, respectively (MES-SA, MES-SA/DX5 and SKN cell lines) and the dasatinib IC50 was 6.68,17.30 and 6.25 µmol/l, respectively. Our findings demonstrate that 15d-PGJ2 suppresses proliferation by inactivating the AKT pathway in uterine sarcoma. Furthermore, combining 15d-PGJ2 with dasatinib produced a synergistic effect on cancer cell inhibition by repressing 15d-PGJ2-mediated activation of MAPK signaling, and further repressing AKT signaling. These results suggest that 15d-PGJ2 could be used in combination with dasatinib as a potential therapeutic approach for uterine sarcoma.

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling in vitro. Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 µM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.