Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 1336-1342, 2007.
Article
Dans En
| WPRIM
| ID: wpr-280437
Responsable en Bibliothèque :
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide (DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.</p><p><b>METHODS</b>DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n = 29) were divided into 4 groups normal saline (NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.</p><p><b>RESULTS</b>DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P < 0.05) without causing weight loss (P > 0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice exhibited a markedly higher apoptotic index compared with control tumors. Western blot analysis of tumor tissue revealed that the down-regulated expression of proliferation cell nuclear antigen (PCNA) and Bcl-2 proteins in DATS-PBCA-NP group, and there were no significant differences in the expression of Fas, FasL and Bax proteins among the four groups (P > 0.05).</p><p><b>CONCLUSIONS</b>DATS-PBCA-NP has good prolonged release effect in vivo and hepatic-targeted activity, and significant anti-tumor effect on the orthotopic transplantation HCC model in mice in association with the suppression of proliferation and the induction of apoptosis of tumor cells. These advantages are probably due to their liver targeting characteristics and consequently bring a higher anti-tumor activity.</p>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Sulfures
/
Transplantation hétérologue
/
Régulation négative
/
Technique de Western
/
Apoptose
/
Antigène nucléaire de prolifération cellulaire
/
Protéines proto-oncogènes c-bcl-2
/
Lignée cellulaire tumorale
/
Traitement médicamenteux
/
Enbucrilate
Type d'étude:
Prognostic_studies
Limites du sujet:
Animals
/
Humans
/
Male
langue:
En
Texte intégral:
Chinese Medical Journal
Année:
2007
Type:
Article