title: Sinomenine sensitizes multidrug-resistant colon cancer cells (Caco-2) to doxorubicin by downregulation of MDR-1 expression.
abstract: Chemoresistance in multidrug-resistant (MDR) cells over expressing P-glycoprotein (P-gp) encoded by the MDR1 gene, is a major obstacle to successful chemotherapy for colorectal cancer. Previous studies have indicated that sinomenine can enhance the absorption of various P-gp substrates. In the present study, we investigated the effect of sinomenine on the chemoresistance in colon cancer cells and explored the underlying mechanism. We developed multidrug-resistant Caco-2 (MDR-Caco-2) cells by exposure of Caco-2 cells to increasing concentrations of doxorubicin. We identified overexpression of COX-2 and MDR-1 genes as well as activation of the NF-κB signal pathway in MDR-Caco-2 cells. Importantly, we found that sinomenine enhances the sensitivity of MDR-Caco-2 cells towards doxorubicin by downregulating MDR-1 and COX-2 expression through inhibition of the NF-κB signaling pathway. These findings provide a new potential strategy for the reversal of P-gp-mediated anticancer drug resistance.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Duan
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jiu-Yang
authors.initials: JY
authors.lastname: Chang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Ke-Hang
authors.initials: KH
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Guang-Quan
authors.initials: GQ
authors.lastname: Mo
authors.affiliation: Department of Neurosurgery, Zhongshan Affiliated Hospital of Dalian University, Dalian, Liaoning, China.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Chang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D018938:Caco-2 Cells; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009019:Morphinans / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D009019:Morphinans; D016328:NF-kappa B; D011720:Pyrazoles; D013449:Sulfonamides; C009271:sinomenine; D004317:Doxorubicin; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone