Inhibitory effect of PD98059 on MAPK signaling pathway in acute lymphocytic leukemia cells / 中国实验血液学杂志

This study was purposed to investigate the effect of blocking Ras/Erk signaling pathway on expression of important transcription factor c-fos, c-jun and TAK1 gene in primary acute lymphocytic leukemia (ALL) cells. The best effective concentration and effect time of PD98059 were screened; the expression levels of c-fos, c-jun and TAK1 in primary cultured cells of normal persons, primary cultured ALL cells and primary cultured ALL cells treated by PD98059 were detected by SYBR GreenI real-time quantitative-PCR. The results showed that before treatment by PD98059 the expression levels of c-fos and TAK1 mRNA were significantly up-regulated in primary cultured ALL cells as compared with primary cultured cells of normal persons (P = 0.014 and P = 0.017 respectively). After treatment by PD98059, the expression levels of c-fos, c-jun mRNA decreased in all 7 serum samples, while expression of TAK1 was down-regulated in 5 samples, and up-regulated in 2 samples. After treatment with PD98059, there was no statistical difference of c-fos, c-jun and TAK1 expression levels in primary cultured ALL cells and primary cultured normal cells. It is concluded that the c-fos and TAK1 activity of primary cultured ALL cells increases, and blocking the Ras/Erk signaling pathway of ALL cells can lead to obvious decrease of important transcription factors c-fos, c-jun, TAK1 genes expression.

Effects of dexamethasone on arsenic trioxide induced apoptosis, NF-kappaB activation and gene expression in lymphoma cell line / 中华血液学杂志

<p><b>OBJECTIVES</b>To study the effect of dexamethasone (Dex) on the apoptosis and NF-kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on apoptosis.</p><p><b>METHODS</b>Cell apoptosis was analysed by Annexin V. Fluctuation of NF-kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry.</p><p><b>RESULTS</b>The apoptosis and activation of NF-kappaB of Raji cells could be induced by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly increased (77.5%) the apoptosis induced by As2O3 (P < 0.05). Dex suppressed the activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P < 0.05). There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB.</p><p><b>CONCLUSIONS</b>As2O3 could induce apoptosis, activate NF-kappaB and up-regulate expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by Dex may be related to suppressing activation of NF-kappaB and down-regulating expression of MMP9 and VEGF.</p>

Arsenic trioxide induced leukemic cell apoptosis relative to NF-kappaB activation / 中国实验血液学杂志

To investigate the relationship of As(2)O(3)-induced leukemic cell apoptosis with NF-kappaB activation and expression of VEGF, MMP9, apoptosis of K562-n cells induced by As(2)O(3) was analyzed by Annexin V, the dynamic changes of NF-kappaB, MMP9 and VEGF expressions were detected by immunohistochemistry. The results showed that activity of NF-kappaB could be increased, accompanied by higher level of expression of MMP9 and VEGF when apoptosis of K562-n cells was induced by As(2)O(3). Dexamethasome not only increased significantly the apoptotic rate, but also suppressed the activation of NF-kappaB of K562-n cells induced by As(2)O(3). Furthermore, there was a positive correlation between the expression of MMP9, VEGF and the activity of NF-kappaB. It is concluded that As(2)O(3) can induce apoptosis, in the meanwhile, activate NF-kappaB and up-regulate expression of MMP9 and VEGF in K562-n cell line. The mechanism of apoptosis of K562-n cells enhanced by dexamethasome may be related to suppression of the activation of NF-kappaB and expression of MMP9 and VEGF.