[Sodium butyrate-induced expression of lung resistance-related gene in human myeloid leukemia K562 cells].
OBJECTIVE
Overexpression of lung resistance-related protein(LRP) is involved in multidrug resistance and poor outcome in acute leukemia. This study was designed to investigate the effect of sodium butyrate (NaB) on LRP expression level and the function of LRP in K562 cells.


METHODS
Human myeloid leukemia K562 cells, used as an in vitro model, were treated with NaB. The LRP mRNA expression and protein levels in the cells before and after NaB treatment were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry indirect immunofluorescence method,respectively. Intracellular Adriamycin(ADM) location and intracellular daunorubicin(DNR) accumulation were detected by fluorescence microscope and flow cytometry, respectively.


RESULTS
Compared with untreated K562 cells, the LRP mRNA level in the cells treated with 2 mmol/L NaB was increased obviously; the protein expression were turned from negative result to positive result and the ratios of positive cells were increased from 1.68% to 35.81%. Intracellular DNR accumulation was decreased in the treated K562 cells and the mean fluorescence of DNR reduced 68.64% compared with the untreated K562 cells. There was strong ADM fluorescence in the nuclei of untreated K562 cells; while the treated K562 cells showed significantly less ADM fluorescence in their nuclei but more fluorescence in the cytoplasm.


CONCLUSIONS
Both the mRNA level and the protein expression of LRP in K562 cells can be increased by NaB induction. LRP induced by NaB is involved in the decreasing anti-cancer drug accumulation and transporting the drugs from the nucleus to the cytoplasm in K562 cells.
Li
Ning
N
Department of Pediatrics, Nanfang Hospital, The First Military Medical University, Guangzhou, Guangdong, 510515, PR China. ningli_cn@yahoo.com
Qian
Xin-Hua
XH
Yao
Ying-Min
YM
Wang
Zhi-Yuan
ZY
D002087:Butyrates / Q000494:pharmacology*; D004317:Doxorubicin / Q000493:pharmacokinetics; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
D002087:Butyrates; D004317:Doxorubicin; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein