@Article{096504016X14772315906527,
AUTHOR = {Jinhui Wu, Dongshuang Wang},
TITLE = {CLIC1 Induces Drug Resistance in Human Choriocarcinoma  Through Positive Regulation of MRP1},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {6},
PAGES = {863--871},
URL = {http://www.techscience.com/or/v25n6/56868},
ISSN = {1555-3906},
ABSTRACT = {Chemotherapy is typically used to treat choriocarcinoma. However, a small proportion of this malignancy 
develops resistance to common chemotherapeutic drugs such as methotrexate (MTX) and floxuridine (FUDR). 
This study aimed to investigate the role and potential mechanisms of chloride intracellular channel protein 1 
(CLIC1) in the development of chemoresistance in choriocarcinoma JeG3 cells. Two chemoresistant sublines 
were induced from their parental cell line JeG3 through intermittent exposure to MTX (named JeG3/MTX) or 
FUDR (named JeG3/FUDR). It was found that expression of CLIC1 was significantly higher in the chemoresistant sublines JeG3/MTX and JeG3/FUDR than in their parental cell line JeG3. Knockdown of CLIC1 by 
specific siRNA significantly increased cell sensitivity to MTX and FUDR in vitro and in vivo. Moreover, the 
high expression of CLIC1 in chemoresistant sublines was associated with upregulation of multidrug resistanceassociated protein 1 (MRP1). Knockdown of CLIC1 decreased the expression of MRP1 accordingly. While 
reexpression of CLIC1 in the parental cell JeG3 increased its resistance to MTX and FUDR, depletion of 
MRP1 significantly blunted CLIC1 reexpression-mediated acquirement of chemoresistance in JeG3 cells. In 
conclusion, our results suggest that CLIC1 may serve as a critical mediator of chemoresistance in human 
choriocarcinoma JeG3 cells. The CLIC1-mediated chemoresistance is achieved through positive regulation of 
MRP1. Depletion of either CLIC1 or its downstream MRP1 may be a promising therapeutic strategy concerning reversing the chemoresistance in human choriocarcinoma JeG3 cells.},
DOI = {10.3727/096504016X14772315906527}
}