Department of Obstetrics and Gynaecology, Osaka City University Graduate School of Medicine, Osaka, 545-8585, Japan.
Anticancer Res. 2011 Apr;31(4):1271-7.
Claudin-4, a component of the tight junction, plays an important role in tumorigenesis and metastasis of ovarian cancer, but its role in platinum resistance has not been elucidated.
Claudin-4 expression in ovarian cancer cells was inhibited and the changes in cisplatin sensitivity were examined. Fluorescence-labeled cisplatin was used to examine whether inhibition of claudin-4 changed the cellular accumulation of cisplatin. Claudin-4 expression in ovarian cancer tissue resected from the patients surgically was evaluated immunohistochemically.
Suppression of claudin-4 resulted in a significant increase of cisplatin sensitivity and cellular accumulation of fluorescence-labeled cisplatin. Claudin-4 expression was significantly greater in ovarian cancer tissue from chemoresistant patients compared to chemosensitive patients. The overall survival was significantly shorter for claudin-4-positive than claudin-4-negative cases.
These data suggest that claudin-4 contributes to platinum resistance in ovarian cancer and may be a potential target in the treatment of platinum-resistant tumors.
紧密连接的组成部分 Claudin-4 在卵巢癌的发生和转移中起着重要作用，但它在铂类耐药中的作用尚未阐明。
抑制卵巢癌细胞中 Claudin-4 的表达，并检测顺铂敏感性的变化。使用荧光标记的顺铂来检测 Claudin-4 的抑制是否改变了顺铂在细胞内的蓄积。用免疫组织化学方法评估从手术切除的卵巢癌组织中 Claudin-4 的表达。
Claudin-4 的抑制导致顺铂敏感性显著增加和荧光标记的顺铂在细胞内蓄积增加。Claudin-4 在耐药患者的卵巢癌组织中的表达明显高于敏感患者。Claudin-4 阳性的病例总生存时间明显短于 Claudin-4 阴性的病例。
这些数据表明 Claudin-4 有助于卵巢癌对铂类的耐药性，并且可能是治疗铂类耐药肿瘤的潜在靶点。
