Reference - Detail
|Author||Yoshida H, Sumi T, Zhi X, Yasui T, Honda K, Ishiko O.|
|Title||Claudin-4: a potential therapeutic target in chemotherapy-resistant ovarian cancer.|
BACKGROUND: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.
MATERIALS AND METHODS: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.
RESULTS: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.
CONCLUSION: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.
|MeSH||Adenocarcinoma, Clear Cell / drug therapy Adenocarcinoma, Clear Cell / metabolism Adenocarcinoma, Clear Cell / pathology Adenocarcinoma, Mucinous / drug therapy Adenocarcinoma, Mucinous / metabolism Adenocarcinoma, Mucinous / pathology Antineoplastic Agents / therapeutic use* Cell Line, Tumor Cisplatin / therapeutic use* Claudin-4 Cystadenocarcinoma, Serous / drug therapy Cystadenocarcinoma, Serous / metabolism Cystadenocarcinoma, Serous / pathology Drug Resistance, Neoplasm* Endometrial Neoplasms / drug therapy Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology Female Fluorescent Antibody Technique Humans Immunoenzyme Techniques Membrane Proteins / metabolism* Middle Aged Ovarian Neoplasms / drug therapy* Ovarian Neoplasms / metabolism* Ovarian Neoplasms / pathology Survival Rate Treatment Outcome|
|Human and Animal Cells||NIH:OVCAR-3 (RCB2135)|