Mechanism of VEGF expression and secretion in HL-60 cells induced by all-trans refinoic acid / 国际肿瘤学杂志

ABSTRACT

Objective To explore molecular mechanism of expression of vascular endothelial growth factor (VEGF) mRNA and secretion of VEGF protein in HL-60 cells induced by all-trans refinoic acid (ATRA). Methods MTr method was used to detect the proliferation of HL-60 cells induced by ATRA,cell cycle and CD11b expression in HL-60 cells were detected by flow cytometry. Expression of VEGF, c-myc, by-poxia-inducible factor(HIF)-lα, matrix metalloproteinase (MMP)-9 and MMP-2 mRNA were detected by semi-quantitative RT-PCR. VEGF protein in HL-60 cells culture supernatant was measured by ELISA before and after being induced by ATRA. Results After treatment with ATRA,the proliferation of HL-60 cells was obviously inhibited, CD11b expression increased, trend of granulocyte directional differentiation emerged, and differentiation degree was increasd(P <0. 05) ;expression level of c-my and VEGF mRNA was down-regulated (P < 0. 05), but expression level of HIF-1α mRNA was up-regulated (P < 0. 05). VEGF protein level in HL-60 cells culture supernatant was decreased by blocking the expression of MMP-9 or MMP-2(P <0. 05).Conclusion VEGF expression has positive correlation with c-myc expression,but has negative correlation with HIF-1α expression. MMP-9 and MMP-2 may be the main factors regulating VEGF secretion in HL-60 cells.