High Expression of Nuclear Transcription Factor-κB is Associated with Cisplatin Resistance and for Ovarian Cancer

Background: Abnormal activation of the nuclear transcription factor-kappa B (NF-kappa B) signaling pathway plays a crucial role in the chemoresistance of tumor cells. This study aimed to explore the significance of NF-kappa B in the chemoresistance of ovarian cancer. Materials: We performed immunohistochemical staining for evaluating the expression of NF-kappa B in cancer tissues. The MTT assay was performed for analyzing cell proliferation, Western blotting was performed to quantify NF-kappa B p65, and flow cytometry was used to determine the apoptosis rate. Results: Nuclear NF-kappa B p65 over-expression was closely associated with ovarian cancer with advanced FIGO stage, residual disease 1 cm and absence of lymph node (LN) metastasis were associated with platinum sensitivity. In multivariate logistic regression, residual disease 1 cm was a risk factor for response to chemotherapy, while the over-expression of nuclear NF-kappa B p65 was a risk factor for sensitivity to chemotherapy. In the ROC curves, nuclear NF-kappa B p65 expression had the discriminative ability for sensitivity to chemotherapy (AUC = 0.637, P = 0.021). Furthermore, nuclear NF-kappa B p65 expression was an independent prognostic factor. Western blotting showed that NF-kappa B p65 level in cisplatin-resistant cells (C13* and A2780cp) was significantly higher than that in cisplatin-sensitive cells (OV2008 and A2780s) (P < 0.05), and this increased expression could be suppressed by NF-kappa B inhibitor PDTC treatment. The proliferation inhibitory rates of cisplatin in C13* and A2780cp cells increased after PDTC treatment in a concentration-dependent manner. PDTC treatment could also enhance cisplatin-induced apoptosis. Conclusion: NF-kappa B was associated with the clinicopathological features, chemoresistance, and prognosis of ovarian cancer. The NF-kappa B inhibitor PDTC can enhance cisplatin sensitivity of platinum-resistant C13* and A2780cp ovarian cancer cells.