Experimental study of the function and mechanism combining dihydroartemisinin and gemcitabine in treating pancreatic cancer / 中华外科杂志
Chinese Journal of Surgery
; (12): 530-534, 2010.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-360745
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the anti-tumor activity of combined gemcitabine with dihydroartemisinin, and the mechanism of the anti-tumor effect of gemcitabine enhanced by dihydroartemisinin on pancreatic cancer.</p><p><b>METHODS</b>For cultured cells, cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis and confocal laser scanning microscope stained with Annexin V-FITC/PI. The nuclear extract for determining NF-kappaB DNA-binding activity was analyzed by EMSA, while nuclear P65 and its downstream gene expression was determined by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to agents. TUNEL assay was used to assess tumor cell apoptosis in tumor tissue.</p><p><b>RESULTS</b>After combination of gemcitabine and dihydroartemisinin treatment, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and Panc-1 reached up to (81.1 +/- 3.9)% and (76.5 +/- 3.3)%, and the apoptosis rates were up to (53.6 +/- 3.8)% and (48.3 +/- 4.3)%, the differences were significantly (P < 0.01) compared with gemcitabine [(24.8 +/- 2.9)% and (21.8 +/- 3.5)%]. All the treatment groups inhibited the growth of pancreatic xenograft tumors in nude mice. The tumor volume and apoptosis index were (262 +/- 37) mm(3) and (50 +/- 4)% respectively in the combined treatment, compared to those of [(384 +/- 56) mm(3) and (25 +/- 3)%] in gemcitabine, the differences were significantly (P < 0.05). EMSA showed that gemcitabine alone obviously enhanced its DNA-binding activity compared to control. However, dihydroartemisinin significantly reduced its DNA-binding activity, so that abrogated the inducing effect of gemcitabine on NF-kappaB activation. Western blot assay indicated that dihydroartemisinin downregulated expression of nuclear P65, and combined treatment not only downregulated the expression of Cyclin D1, Bcl-xL and Bcl-2 while upregulated Bax, thus reduced the Bcl-2/Bax ratio, but also increased the caspase-3 activation, all of which increased apoptosis in both BxPC-3 and Panc-1 cells.</p><p><b>CONCLUSION</b>Dihydroartemisinin significantly abrogated the inducing effect of gemcitabine on NF-kappaB activation and downregulated the expression of NF-kappaB targeted gene products, which may be one possible mechanism by which dihydroartemisinin augments the anti-tumor effect of gemcitabine on pancreatic cancer.</p>
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Doenças do Sistema Endócrino
/
Neoplasia Pancreática
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Neoplasias Pancreáticas
/
Patologia
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
NF-kappa B
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Apoptose
/
Ensaios Antitumorais Modelo de Xenoenxerto
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Artemisininas
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Linhagem Celular Tumoral
/
Usos Terapêuticos
/
Desoxicitidina
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Chinês
Revista:
Chinese Journal of Surgery
Ano de publicação:
2010
Tipo de documento:
Artigo