Inhibition of hypoxia-inducible factor-1 alpha in RPMI8226 myeloma cells results in reduced tumor growth in nude mice / 中华血液学杂志
Chinese Journal of Hematology
; (12): 247-251, 2008.
Article
em Zh
| WPRIM
| ID: wpr-240029
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WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore the influence of inhibition of hypoxia-inducible factor-1 alpha (HIF-1 alpha) by RNA interference (RNAi) on tumorigenesis of human myeloma cell line (HMCL) RPMI8226 cells in nude mice.</p><p><b>METHOD</b>RNAi vector of HIF-1 alpha was constructed with commercial shRNA expression vector pSilencer 2. 1-U6 hygro. RT-PCR and western blot were used to detect HIF-1 alpha mRNA and protein expression respectively. Vascular endothelial growth factor (VEGF) secretion and cell cycle changes were detected by ELISA and flow cytometry respectively. Expression of target gene of HIF-1 alpha, VEGF and Glut-1 were tested under hypoxia condition. Tumorigenesis was observed after transfected cells were injected subcutaneously in nude mice.</p><p><b>RESULTS</b>After interference, expression of HIF-1 alpha decreased significantly at both mRNA and protein level. Under normoxia condition, VEGF concentrations in HIF-la inhibited cells (RPMI8226-il and RPMI8226-i2) and non-inhibited cells (RPMI8226-c and RPMI8226) showed no differences. While under hypoxia condition, VEGF concentration in the above four cells was (506.0 +/- 53.2), (494.7 +/- 63.1), (984.4 +/- 61.9) and (938.2 +/- 62.2) pg/ml, respectively, being significantly lower in RPMI8226-il and RPMI8226-i2 cells than in RPMI8226-c and RPMI8226 cells (P <0.05). HIF-1 alpha interference was found to suppress the cells shift from S-phase to G1 induced by hypoxia. VEGF and Glut-1 expressions were markedly attenuated (P <0.05). The growth rate of HIF-1 alpha inhibition tumors in subcutaneous xenograft model decreased drastically.</p><p><b>CONCLUSIONS</b>RNAi inhibits HIF-1 alpha expression. Reduced tumor growth by HIF-1 alpha inhibition may partly through inhibiton of angiogenesis and glycolysis metabolism.</p>
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Índice:
WPRIM
Assunto principal:
Patologia
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Ciclo Celular
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Ensaios Antitumorais Modelo de Xenoenxerto
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Interferência de RNA
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Linhagem Celular Tumoral
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Fator A de Crescimento do Endotélio Vascular
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Transportador de Glucose Tipo 1
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Vetores Genéticos
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Genética
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
Zh
Revista:
Chinese Journal of Hematology
Ano de publicação:
2008
Tipo de documento:
Article