Expression of NLK and Its Potential Effect in Ovarian Cancer Chemotherapy

Objective: This study aimed to investigate the expression of NLK in ovarian cancer tissue and whether the proposed apoptosis induced by NLK was involved in ovarian cancer cells sensitive to cisplatin.

Methods: Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 60 cases of ovarian carcinoma. Mantel-Haenzel test or Fisher exact test was used to analyze the correlation between NLK and clinicopathological parameters. Survival analyses were performed by the Kaplan-Meier method. Cisplatin was used to induce apoptosis of the ovarian cancer cell line SKOV3. NLK was stably overexpressed and/or knockdown in SKOV3 cells, and then the effect of the p38 inhibitor SB203580 in combination with cisplatin on SKOV3 cell growth characteristics was tested.

Results: Low NLK expression was observed in 60 ovarian cancer specimens. And it was related to the stage (P = 0.018) and histologic grade (P < 0.001) according to the International Federation of Gynecology and Obstetrics classification. Kaplan-Meier analysis revealed that low NLK expressions were significantly associated with poor prognoses of the patients (P < 0.01). In the cisplatin-treated cells, the expression of NLK was decreased, gradually through p38 signal pathway. Overexpression NLK could enhance cell sensitive to cisplatin.

Conclusions: NLK expression was suppressed in the development of ovarian cancer, and low NLK protein expression might be related to poor outcome. In the chemotherapy for ovarian cancer, cell apoptosis induced by cisplatin was dependent on the NLK expression. In a word, NLK may be a useful prognostic marker and target in ovarian cancer.