title: [Inhibitory effect of pyrrolidine dithiocarbamate combined with matrine on the growth of human hepatocellular carcinoma xenografts].
abstract: OBJECTIVE
  To investigate the relationship between activation of nuclear factor-K-gene binding (NF-κB) and apoptosis induced by matrine(MT) in transplanted tumor of human hepatocellular carcinoma in nude mouse.
  
  
  METHODS
  Tumors were established by injection of hepatocellular carcinoma cell line HepG2 into the back of nude mice. The mice were divided randomly into four groups: Control group, MT group (35 mg/kg), PDTC group (120 mg/kg) and Combination group: PDTC + MT group (120 mg/kg + 35 mg/kg), the reagents were injected peritoneally. The tumor growth curve of nude mice bearing transplanted tumor were observed and the inhibition ratios were evaluated. Apoptosis of carcinoma cells was analyzed by TUNEL. The DNA-binding activity of NF-κB was determined by electrophoretic mobility shift assay (EMSA). Expression of bcl-2 and bax in carcinoma tissue were detected by immunohistochemical method. NF-κB mRNA, bcl-2 mRNA and bax mRNA in carcinoma tissue were detected by RT-PCR.
  
  
  RESULTS
  Pyrrolidine dithiocarbamate (PDTC) could enhance the inhibition of matrine on carcinoma proliferation (P < 0.05). The apoptosis and activation of NF-κB in carcinoma cells could be induced by matrine. PDTC significantly suppressed NF-κB activation induced by matrine in carcinoma cells from 93.64 ± 2.95 to 65.78 ± 5.65 (F = 124.754, P < 0.01). Meanwhile, PDTC increased the apoptosis induced by matrine from 55.9% ± 2.8% to 74.3% ± 4.8% (P < 0.05).A positive correlation observed between the expressions of NF-κB and of bcl-2 (Pearson correlation coefficient = 0.983, P < 0.01).
  
  
  CONCLUSIONS
  Matrine could induce apoptosis and activation of NF-κB in transplanted tumor. PDTC could increase apoptosis in hepatocellular carcinoma cells might be due to the suppression of NF-κB activation and the enhancement of bcl-2 expression.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
authors.forename: Na
authors.initials: N
authors.lastname: Luo
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.forename: Wei-xue
authors.initials: WX
authors.lastname: Tang
authors.forename: Guo-qing
authors.initials: GQ
authors.lastname: Zuo
authors.forename: Yu
authors.initials: Y
authors.lastname: Liao
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D011759:Pyrrolidines / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D016328:NF-kappa B; D011759:Pyrrolidines; D011807:Quinolizines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D000093842:Matrines