title: Neutrophil gelatinase-associated lipocalin regulates intracellular accumulation of Rh123 in cancer cells.
abstract: Multidrug resistance (MDR) is a major problem facing patients with cancer. Although Neutrophil gelatinase-associated lipocalin (NGAL) is highly expressed in various cancers, the possible role of NGAL in MDR is still obscure. In this article, we evaluated the effect of NGAL on Rh123 accumulation in cancer cells. NGAL was first down-regulated by short hairpin RNA-mediated interference. In correlation with the reduced NGAL expression, intracellular Rh123 accumulation was significantly decreased. We finally observed that inhibiting both of the ERK1/2 and p38 MAPK could seriously down-regulate NGAL expression and also decrease the intracellular accumulation of Rh123, indicating that NGAL-mediated Rh123 accumulation is regulated by the phosphorylation of ERK1/2 and p38 MAPK. Pretreatment of MDA-MB-231 with NGAL recombinant protein and antibody had significant effects on the intracellular accumulation of Rh123, whereas little effect was observed in K562 cells treated with the same method, suggesting that NGAL was involved in the regulation of Rh123 accumulation in these two types of cancers, although different pathways. Here we provide new evidence that directly shows the possibility of small chemical substances Rh123 intracellular accumulation that is regulated by NGAL. These results suggest the possibility of NGAL involvement in drug transportation and cancer MDR formation, and indicate the potential of NGAL in cancer therapy.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Wang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chang
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Lin
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Jin
authors.forename: Hua-Wen
authors.initials: HW
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Ruo-Jun
authors.initials: RJ
authors.lastname: Wang
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Li
authors.forename: Tian-Xiang
authors.initials: TX
authors.lastname: Pang
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005456:Fluorescent Dyes / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020112:Rhodamine 123 / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D005456:Fluorescent Dyes; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D020112:Rhodamine 123