title: Suppression of multidrug resistance by rosiglitazone treatment in human ovarian cancer cells through downregulation of FZD1 and MDR1 genes.
abstract: Multidrug resistance (MDR) is a major obstacle in the successful treatment of ovarian cancer. One of the most common causes of MDR is overexpression of P-glycoprotein (P-gp), encoded by the MDR1 gene. The MDR1 gene is a direct target of the Wnt/β-catenin signaling pathway, which plays an important role in ovarian cancer. Peroxisome proliferator-activated receptor γ (PPARγ) ligands have been found to protect against development of cancer through the Wnt/β-catenin pathway. To investigate the effect of PPARγ ligands on MDR1/P-gp expression, we treated a MDR ovarian cancer cell subline, A2780/Taxol, with different concentrations of rosiglitazone (Rosi), a member of the synthetic PPARγ ligands. Rosi downregulated FZD1 and MDR1/P-gp expression in a concentration-dependent manner. In addition, nuclear β-catenin levels and its transcriptional activity decreased significantly. In conclusion, Rosi may reverse MDR of ovarian cancer cells by downregulating the Wnt/β-catenin pathway with the suppression of FZD1.
authors.affiliation: aDepartment of Pathology, Qilu Hospital of Shandong University bDepartment of Pathology, Shandong University School of Medicine, Shandong, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Jing
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D051157:Frizzled Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000813:Anilides; D000970:Antineoplastic Agents; C489740:FZD1 protein, human; D051157:Frizzled Receptors; D047495:PPAR gamma; D045162:Thiazolidinediones; D051153:Wnt Proteins; D051176:beta Catenin; D000077154:Rosiglitazone; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil