title: Downregulation of BMI-1 enhances 5-fluorouracil-induced apoptosis in nasopharyngeal carcinoma cells.
abstract: 5-Fluorouracil (5-FU) is an important chemotherapeutic agent for nasopharyngeal carcinoma (NPC). However, drug resistance may occur after several cycles of 5-FU-based chemotherapy. The oncogene B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) has been shown to be involved in the protection of cancer cells from apoptosis. In this study, 5-FU treatment could increase the percentage of apoptotic NPC cells among BMI-1/RNAi-transfected cells than that among cells transfected with the empty vector. The 50% inhibitory concentration (IC(50)) values of 5-FU were significantly decreased to a greater extent in the cells transfected with BMI-1/RNAi. Most importantly, the expression of phospho-AKT and the anti-apoptotic protein BCL-2 were downregulated in the cells in which BMI-1 expression was inhibited, whereas the apoptosis-inducer BAX was observed to be upregulated. Abrogation of AKT pathway by a PI3K inhibitor could not further increase the sensitivity to 5-FU in the cells with reduced BMI-1 expression. Taken together, BMI-1 depletion enhanced the chemosensitivity of NPC cells by inducing apoptosis; which is associated with inhibition of the PI3K/AKT pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Gui-Xiang
authors.initials: GX
authors.lastname: Weng
authors.forename: Man-Zhi
authors.initials: MZ
authors.lastname: Li
authors.forename: Qing-Li
authors.initials: QL
authors.lastname: Kong
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Li-Bing
authors.initials: LB
authors.lastname: Song
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D009687:Nuclear Proteins / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics*; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors
chemical_list: D000964:Antimetabolites, Antineoplastic; C069077:BMI1 protein, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein; D063150:Polycomb Repressive Complex 1; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil