TY - JOUR AB - Ovarian cancer is the most lethal gynecological malignancy, for which platinum- and taxane-based chemotherapy plays a major role. Chemoresistance of ovarian cancer poses a major obstacle to the successful management of this devastating disease; however, effective measures to overcome platinum and taxane resistance are yet to be established. In the present study, while investigating the mechanism underlying the chemoresistance of ovarian cancer, we found that JNK may have a key role in the resistance of ovarian cancer cells to cisplatin and paclitaxel. Importantly, whereas simultaneous application of a JNK inhibitor and either of the chemotherapeutic agents had contrasting effects for cisplatin (enhanced cytotoxicity) and paclitaxel (decreased cytotoxicity), JNK inhibitor treatment prior to chemotherapeutic agent application invariably enhanced the cytotoxicity of both drugs, suggesting that the basal JNK activity is commonly involved in the chemoresistance of ovarian cancer cells to cisplatin and paclitaxel in contrast to drug‑induced JNK activity which may have different roles for these two drugs. Furthermore, we confirmed using non-transformed human and rodent fibroblasts that sequential application of the JNK inhibitor and the chemotherapeutic agents did not augment their toxicity. Thus, our findings highlight for the first time the possible differential roles of the basal and induced JNK activities in the chemoresistance of ovarian cancer cells and also suggest that time‑staggered JNK inhibition may be a rational and promising strategy to overcome the resistance of ovarian cancer to platinum- and taxane-based chemotherapy. AD - Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata 990‑9585, Japan Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata 990‑9585, Japan AU - Seino,Manabu AU - Okada,Masashi AU - Sakaki,Hirotsugu AU - Takeda,Hiroyuki AU - Watarai,Hikaru AU - Suzuki,Shuhei AU - Seino,Shizuka AU - Kuramoto,Kenta AU - Ohta,Tsuyoshi AU - Nagase,Satoru AU - Kurachi,Hirohisa AU - Kitanaka,Chifumi DA - 2016/01/01 DO - 10.3892/or.2015.4377 EP - 601 IS - 1 JO - Oncol Rep KW - ovarian cancer combination chemotherapy JNK pretreatment co-treatment PY - 2016 SN - 1021-335X 1791-2431 SP - 593 ST - Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel T2 - Oncology Reports TI - Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel UR - https://doi.org/10.3892/or.2015.4377 VL - 35 ER -