Pegylated liposomal­paclitaxel induces ovarian cancer cell apoptosis via TNF­induced ERK/AKT signaling pathway.

ABSTRACT

Ovarian cancer is one of the most common gynecological types of cancer and is characterized by a relatively high incidence and high mortality rate. Evidence has demonstrated that paclitaxel (PTX) is an effective therapeutic treatment for human ovarian cancer. In the present study, the inhibitory effects of pegylated liposomal (PL)­PTX on the growth of ovarian cancer cells were investigated in vitro; a CAOV­3­bearing mouse model was established to investigate the in vivo effects of PL­PTX on ovarian tumor growth. In the present study, the underlying mechanism of tumor necrosis factor (TNF)­induced inhibition of extracellular signal­regulated kinase (ERK)/protein kinase B (AKT) signaling pathway mediated by PL­PTX was analyzed within ovarian cancer cells. The results of the present study revealed that PL­PTX significantly inhibited the growth and aggressiveness of ovarian cancer cells in vitro and in vivo and apoptotic ability increased upon administration of PL­PTX. The expression levels of caspase­3/9 were significantly upregulated within PL­PTX­treated ovarian cancer cells. The expression and phosphorylation levels of ERK and AKT were markedly increased in response to PL­PTX treatment. In addition, the inhibitory effects of PL­PTX on ovarian cancer cells were eliminated by neutralizing antibodies against TNF. The observations of the present study revealed that PL­PTX induced ovarian cell apoptosis via the TNF­dependent pathway, which was significantly inhibited with the employment of antibodies against TNF. In vivo analysis demonstrated that PL­PTX treatment significantly inhibited ovarian tumor growth and prolonged the survival of tumor bearing mice. In conclusion, the findings of the present study have provided an insight into the potential mechanism of PL­PTX­induced apoptosis of ovarian cancer cells. As PL­PTX has been reported to induce ovarian tumor cell apoptosis via the TNF­induced ERK/AKT signaling pathway, PL­PTX may serve as an efficient anticancer drug for the treatment of ovarian cancer.