The
paclitaxel/cisplatin combination
therapy commonly is used as the first-line treatment for advanced
ovarian cancer patients.
Midkine (MK), known as a novel
tumor biomarker, has been elevated in the serum of patients with
epithelial ovarian cancer (EOC). In this study, we aimed to detect the expression of MK in EOC tissues and evaluate clinical value of MK in diagnosis and
therapy of EOC. We perform immunohistochemistry analysis to detect MK in EOC sample with postoperative
platinum/
paclitaxel combination
therapy, we found that 71.4% (85 in 119 samples) of these samples were MK positive (> 10% of the cells were stained), and the expression of MK was significantly associated with disease histology (P = 0.038) as well as differentiation grade (P < 0.001). Moreover, MK positive samples show much more sensitive to
cisplatin/
paclitaxel combination
therapy, compared with MK negative samples (P = 0.029). Those results indicated that MK expression might correlate with
paclitaxel and/or
cisplatin cytotoxicity in clinical
therapy of EOC. Then, we evaluated the sensitivity to
cisplatin and
paclitaxel in 5
ovarian cancer cell lines (ES2, A2870, HO-8910, SKOV3 and SW626), and ES2, the highest MK expression among those cell lines, show the most sensitive to
paclitaxel and
cisplatin. Further, we confirmed this correlation between MK and
paclitaxel and/or
cisplatin cytotoxicity with the gain- and lost- of function. Finally, we demonstrated that MK enhanced the cytotoxicity of
paclitaxel and/or
cisplatin by accumulated
cisplatin and
paclitaxel through inhibited the expression of
multidrug resistance-associated protein 3 (MRP3). In conclusion, MK could be an effective
biomarker in diagnosis and
therapy of EOC, especially for the
drug selection at the time of initial diagnosis.