HtrA2/Omi protease in epithelial ovarian carcinoma: clinical significance and antineoplastic efficacy of its overexpression on subcutaneous transplanted tumor in nude mice model

The serine protease HtrA2/Omi, a regulator of apoptosis, is localized in mitochondria and is released into the cytosol after apoptotic stimuli. Previous studies demonstrate that Omi/HtrA2 is associated with a variety of malignancies. In the present study, we analyzed the expression of Omi/HtrA2 in 52 epithelial ovarian carcinoma (EOC) tissues and paired corresponding adjacent non-tumor tissues to elaborate the clinical significance and antineoplastic efficacy of Omi/HtrA2 on subcutaneous transplanted tumor in a nude mice model. The results showed that the mRNA and protein expression of Omi/HtrA2 in the EOC tissues was dramatically higher than that in the adjacent non-tumor tissues, and Omi/HtrA2 was highly correlated with clinicopathological parameters, such as clinical stage and distant metastasis. Moreover, HtrA2/Omi gain-of function acute and HtrA2/Omi loss-of function blunted apoptosis in A2780 and OVCAR-3 cell lines. In vivo, HtrA2/Omi gain-of function could attenuate A2780and OVCAR3-engrafted tumors growth and increase the protein expression of caspase3 and caspase9 in engrafted tumors mice as compared to the control group. In conclusion, these results suggested that overexpressed HtrA2/Omi could inhibit EOC cell growth in vitro and in vivo, and the underlying mechanism was mediated, at least partially, through the activation of caspase3 signaling pathway.