| Many experiments in vitro and clinic researches had shown that arsenic trioxide can induce apoptosis of acute promyelocytic leukemia (APL) cells. Arsenic trioxide had also shown satisfactory curative effects on patients with primary and relapsing APL clinically. Recently, arsenic trioxide was found to be capable of inducing apoptosis of cell lines those origin from myeloblastic, lymphoblastic, megakaryocytic and plasmocytic malignant hematological diseases. But there are few reports of effects of arsenic trioxide on T lymphoblastic leukemia cell lines. Here we investigated effects of arsenic trioxide on Jurkat and Molt-4 cells, two kinds of human T lymphoblastic leukemia cell lines, and mechanisms involved, which are expected to provide theoretic basis for expanding the therapeutic spectrum of arsenic trioxide.The effective plasma concentrations of arsenic trioxide, which are from 2u mol/L to 6u mol/L, were selected for experimental use. MTT method was used to investigate the growth inhibition of arsenic trioxide on Molt-4 and K562 cells. We found that 50% inhibiting concentration (IC50) of arsenic trioxide was 4. 68 n mol/L for Molt-4 cells and only 2. 78 u mol/L for K562 cells. When the concentration varied from 2 u mol/L to 6u mol/L, the inhibitory action of arsenic trioxide on Molt-4 cells had time and dose dependent pattern. Further studies showed that Molt-4 cells were arrested in Gl and/or G2-M phases, and the proportion of Molt-4 cells inS phase also decreased after arsenic trioxide treatment. These results indicated that Gl and/or G2-M arrests played important role in the mechanism. The alteration of sub Gl peaks of Molt-4 cells were detected with FACS, and results revealed that 2nmol/L of arsenic trioxide can induce the apoptosis of Molt-4 cells, 4umol/L and 6umol/L showed more significant effects, which indicated that arsenic trioxide at clinically therapeutic levels can induce effective apoptosis of Molt-4 cells. To compare the apoptosis-inducing effects of arsenic trioxide on lymphoblastic and myeloblastic cells, we also chose K562 cells as research target. We found that the apoptotic rates of K562 and Molt-4 cells were 83. 44%?8. 04% and 77. 93%?% respectively after treated with 6umol/L arsenic trioxide for 96 hours. In contrast with K562 cells, Molt-4 cells had similar sensitivity to arsenic trioxide, while Jurkat cells had less, which accorded with reports before'1"4'. These results indicated that arsenic trioxide may play important role in treatment of some types of T lymphoblastic leukemia.Studies in vitro had shown that caspase (Cysteinyl aspartate-specif ic protease) was important target of arsenic trioxide. FACS and Western blot were used to detect active caspase 3 expression of Molt-4 and K562 cells after treatment of arsenic trioxide. There was no significant change of active caspase 3 expression of Molt-4 cells after treated with arsenic trioxide at various doses for 48 and 72 hours, while there was significant up-regulation in K562 cells. Results of Western blot also supported this opinion. These results indicated that mechanisms involved in the apoptosis of T lymphoblastic leukemia induced by arsenic trioxide was independent of caspase-3. It was different from myeloblastic leukemia. Further researches showed that caspase 3 inhibitor Z-DEVD-FMK had no inhibition effects on the apoptosis of Molt-4 cells induced by arsenic trioxide on 48 and 72 hours, which supported the caspase 3 independent apoptosis of T lymphoblastic leukemia cell lines by arsenic trioxide.Recently, the structural integrity and function of telomere are found to play important role on maintaining the proliferation of tumor cells, even more than the length of telomere. Herein telomere repeat-binding factor 2(TRF2) is very important. In experiments in vitro, the inhibition of TRF2 can result in the loss of G-tail of telomere end and thereforeinduce the fusion of chromosome15'. Overexpression of TRF2 can recruit many related proteins to protect telomere and inhibit the senescence of cells. In additio...
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