Downregulation of ITIH3 contributes to cisplatin‑based chemotherapy resistance in ovarian carcinoma via the Bcl‑2 mediated anti‑apoptosis signaling pathway

. Platinum resistance of ovarian cancer is one of the primary factors of poor prognosis and inter‑ α ‑trypsin inhibitor heavy chain 3 (ITIH3) is a potential DDP resistance‑associ‑ ated gene. The present study assessed protein expression levels of ITIH3 in human ovarian cancer and evaluated the relationship between its expression and platinum‑resistance in patients. Furthermore, the effect of ITIH3 on cisplatin (DDP)‑resistant ovarian cancer cells and the underlying molecular mechanism were evaluated. Tissue microarrays of ovarian cancer samples were used to assess the association between ITIH3 protein expression levels and drug resistance and the prognosis of ovarian cancer. ITIH3 RNA interfer‑ ence (RNAi) ovarian cancer cell lines were constructed and expression levels of anti‑ and pro‑apoptotic proteins of the Bcl‑2 associated pathway, including Bcl‑2, Bcl‑xL, Mcl‑1, Bak, Bim, Bax, caspase 3 and poly ADP‑ribose polymerase (PARP), were assessed following DDP treatment. The Bcl‑2 inhibitor ABT‑737 was used to rescue DDP‑resistance induced by loss of ITIH3 in vitro . Finally, a subcutaneous xenograft tumor model was used to evaluate the effect of multiple DDP injections on expression levels of apoptosis‑related proteins like Bcl‑2, Bcl‑xL, Bak, caspase 3 and PARP. The results of tissue microarray immunohistochemistry revealed that decreased ITIH3 protein expression levels were associated with a shorter overall survival for patients with ovarian cancer. The results of Cell Counting Kit‑8 assay showed that the half‑maximal inhibitory concentration and resistance index of DDP in