TIPE1 impairs ovarian tumor growth by promoting caspase-dependent apoptosis.

Abstract

Tumor necrosis factor-α-induced protein 8-like 1 (TIPE1) functions as a tumor suppressor in several types of cancer, including lung and breast cancer. The present study aimed to determine the level of expression and the function of TIPE1 in ovarian cancer. TIPE1 expression was determined in tissue microarrays and ovarian cancer cells, and these data were analyzed to assess the association between TIPE1 expression and prognosis in patients with ovarian cancer. The potential antitumor effects of TIPE1 were investigated in vitro and in a xenograft mouse model. Furthermore, the underlying molecular mechanism by which TIPE1 regulates ovarian cancer growth was determined via flow cytometric analysis, western blotting and rescue experiments. The results of the present study indicated that TIPE1 levels were markedly decreased in ovarian cancer tissues, and its level of expression was associated with a favorable prognosis of patients with ovarian cancer. In addition, ectopic TIPE1 expression significantly impaired A2780 and SKOV3 cell proliferation and colony formation in vitro, which was accompanied by efficient inhibition of xenograft tumor growth in mice. Investigations into the underlying molecular mechanism demonstrated that TIPE1 induced ovarian cancer cell apoptosis by promoting caspase protein expression. Inhibition of caspase-dependent apoptosis by z-VAD blocked TIPE1-mediated inhibition of the proliferation and induction of apoptosis in ovarian cancer cells. Collectively, the results of the present study suggest that TIPE1 may be a potential prognostic predictor and therapeutic target for patients with ovarian cancer.