title: [Abnormal expression of circulating nuclear factor-κB in hepatocellular carcinoma and reversal of multidrug resistance through intervening its gene transcription].
abstract: OBJECTIVE
  To investigate the expressions of nuclear factor-κB (NF-κB) and P-glycoprotein (P-gp) in patients with liver diseases and the effects and mechanism of intervening NF-κB activation on multiple drug resistance (MDR) reversal.
  
  
  METHODS
  The levels of circulating NF-κB and P-gp expression were quantitatively detected in 294 patients with liver diseases by using enzyme-linked immunosorbent assay. NF-κB gene transcription in human HepG2 cells was intervened by specific siRNA with/without doxorubicin treatment. Levels of protein or gene expression were analyzed by Western blotting or fluorescence quantitative polymerase chain reaction (PCR).
  
  
  RESULTS
  The dynamic increase of circulating NF-κB and P-gp expressions were observed during patients from chronic hepatitis to cirrhosis to hepatocellular carcinoma (HCC) development. The levels of serum NF-κB and P-gp expression in HCC were significantly higher (P<0.001) than those in cirrhosis, chronic hepatitis, and normal controls. The expression levels of serum NF-κB and P-gp were significantly associated with HBV infection (P<0.05), elevated after interventional chemotherapy with higher frequency or prolonged therapy, and significantly decreased in the post-operative HCC (P<0.001). Both expressions in HepG2 cells were significantly higher after adding doxorubicin in the cell cultures. After the cells were transfected with siRNA, the NF-κB expression was down-regulated at mRNA or protein level with higher sensitivity to doxorubicin.
  
  
  CONCLUSIONS
  The over-expressions of NF-κB and P-gp are closely associated with MDR formation; intervention of NF-κB activation can inhibit P-gp expression, and enhance the sensitivity to anti-cancer drug and reverse MDR of HCC.
authors.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D006528:Carcinoma, Hepatocellular; D015536:Down-Regulation; D004317:Doxorubicin; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D016328:NF-kappa B; D012333:RNA, Messenger; D014158:Transcription, Genetic
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D004317:Doxorubicin