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The aim of this article is to explore the effect of arsenic trioxide (As2O3) on the proliferation and apopto-sis of myeloma cell line U266 and its relationship with the expression variation of vascular endothelial growth factor (VEGF). The viability and apoptosis of U266 cells were observed by methylthiazolyl-tetrazolium (MTT) assay and terminal-deoxynucleotidyi transferase mediated nick end labeling (TUNEL). The effect of As2O3 on the VEGF expression of U266 cells were tested by enzyme linked immunosorbent assay (ELISA) and reverse transcrip-tion-polymerase chain reaction (RT-PCR) analysis. We found that As2O3 could significantly inhibit the growth of U266 cells, and the concentration for 50% growth inhibition (IC50) was 2 umol/L. After treatment with 2, 5, 10 umol/L As2O3 for 36 hours, dose-dependent apop-tosis of U266 cells was observed. After treatment with 2, 5, 10 umol/L As2O3 for 72 hours, a dose-dependent reduc-tion of VEGF in the supeatant of U266 cells culture was found. As far as single cells are conceed, nevertheless, the expression of VEGF mRNA did not vary. So we drawthe conclusion that As2O3 could induce the apoptosis of U266 cells and inhibit their proliferation, decrease the tumor load, and lead to the reduction of VEGF in the culture supeatant, but not change the expression of VEGF in single U266 cells.