Synergism of As2S2 and STI 571 in inducing apoptosis of K562 cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the synergistic effect of As(2)S(2) and STI 571 on K562 cells and its mechanism.</p><p><b>METHODS</b>The inhibitive effect of As(2)S(2) on the proliferation of K562 cells was determined by cell number count. Cell apoptosis was assessed by flow cytometry, DNA fragmentation and morphology. Protein expression was determined by Western-blot and gene expression by RT-PCR.</p><p><b>RESULTS</b>As(2)S(2) could significantly inhibit the proliferation and induce apoptosis of K562 cells in a dose and time-dependent manner at concentrations from 1 micromol/L to 5 micromol/L for 24 approximately 72 h. 34.4%, 21.8% and 46.0% of the treated-cells displayed apoptosis at 3 micro mol/L for 72 h, 5 micromol/L for 48 h and 5 micromol/L for 72 h, respectively. Compared to treatment with STI571 (0.25 approximately 1.00 micromol/L) or As(2)S(2) (1 approximately 5 micromol/L) alone, treatment of K562 cells with As(2)S(2) and STI571 combination induced more cell apoptosis. (18.4 +/- 1.4)% and (15.8 +/- 1.2)% cells underwent apoptosis at 1 micromol/L STI571 for 48 h and 5 micromol/L As(2)S(2) for 48 h, respectively, and (40.6 +/- 2.0)% cells did in combination treatment (P < 0.05). For U937 cells, the percentages of apoptotic cells were (6.0 +/- 1.1)% at 1 micromol/L STI571 for 48 h, (4.5 +/- 1.2)% at 5 micromol/L As(2)S(2) for 48 h, and (7.3 +/- 1.0)% in combination treatment. As(2)S(2) decreased the bcr-abl fusion protein expression and PTK activity of c-abl and bcr-abl, but not for bcr-abl expression.</p><p><b>CONCLUSION</b>Combination treatment with As(2)S(2) and STI 571 induced more apoptosis of K562 cells. The reduction of PTK activity may be involved in the mechanisms.</p>

Preliminary study on the molecular mechanism of K562 cell apoptosis induced by As2S2 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the apoptotic inducing effect of As(2)S(2) on K562 cells.</p><p><b>METHODS</b>The apoptotic inducing effect of As(2)S(2) on K562 cells was determined by flow cytometry, DNA fragmentation analysis and morphology observation. Expression of protein was determined by Western-blot. RT-PCR was used to evaluate changes in gene expression.</p><p><b>RESULTS</b>Apoptosis of K562 cells was induced by 48 - 72 h exposure to 5 micromol/L As(2)S(2). Apoptosis was induced in (34.4 +/- 3.3)% treated cells by 72 h exposure to 3 micro mol/L As(2)S(2), in (21.8 +/- 3.6)% treated cells by 48 h exposure to 5 micromol/L As(2)S(2) and in (46.0 +/- 5.2)% treated cells by 72 h exposure to As(2)S(2) at the same concentration. With 5 micromol/L As(2)S(2), the protein level of Bcr-Abl and JAK2 decreased, while bax expression was upregulated and c-myc was downregulated both in protein and mRNA level. The activity of caspase 3 in K562 cells was increased by As(2)S(2). As(2)S(2) also induced apoptosis of fresh mononuclear cells derived from chronic myelogenous leukemia (CML) patients.</p><p><b>CONCLUSION</b>As(2)S(2) can induce apoptosis of CML cells. The decline of Bcr-Abl may play an important role. The upregulation of bax, increase of the activity of caspase 3, downregulation of c-myc and decrease of JAK2 may also be involved in the mechanism.</p>