SUPPRESSION OF STARD7 DECREASES ABCG2 AND ENHANCES SENSITIVITY TO CHEMOTHERAPY DRUGS IN HUMAN CANCER

FLORES-MARTÍN J; REYNA L; RIDANO ME; PANZETTA-DUTARI GM; GENTI-RAIMONDI S

Rosario, Santa Fé

Congreso; L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2014

Drug resistance during chemotherapy is the major obstacle to the successful treatment of many cancers. Several ABCtransporters have been recognized as a source of drug resistance in the treatment of malignancies. StarD7 is a memberof the START domain superfamily, which is involved in lipid transfer, metabolism, and modulation of signalingpathways. Previous results indicate that StarD7 silencing decreases ABCG2 multidrug transporter level, cellmigration, proliferation, and phospholipid synthesis; whereas an increase in biochemical and morphologicaldifferentiation marker expression was detected in the choriocarcinoma JEG-3 cells. Here, we report that inhibition ofStarD7 by siRNA led to a marked decrease of ABCG2 expression in HepG2 and A549 cell lines. Using flowcytometry and a microplate reader assay, we found that intracellular accumulation of the chemotherapeutic agentmitoxantrone was enhanced in cell lines transfected with StarD7 siRNA. In addition, StarD7 silencing led toincreased ROS basal level as well as ROS-mediated cell toxicity induced by H2O2. More importantly, knockingdown StarD7 resulted in enhanced sensitivity of cancer cells to chemotherapeutic agents. In summary, our results suggest that targeted inhibition of StarD7 may be a novel therapeutic approach to overcome chemoresistance ofepithelial cancer cells.