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Arsenic Trioxide On The Pro-apoptotic In Chronic Myeloid Leukemia Cell Line K562 And Its Mechanism

Posted on:2004-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:Y C WangFull Text:PDF
GTID:2204360092987210Subject:Academy of Pediatrics
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At present, chronic myelogenous leukemia (CML) therapies are mostly consisted of using chemotherapies, interferon and bone marrow transplantation. Recently, STI571 was introduced into the treatment of CML as an effective agent, because it is a specific inhibitor of Bcr/abl tyrosine kinase.lt was reported that this agent was very effective in the treatment of CML at chronic phase, and the adverse effects were mild. However, according to the results of clinical trials, relapse of the disease usually occurs after suspending the treatment, because the malignant colony of the CML cannot be completely eradicated. Therefore, it is very important to find other effective agents for CML therapy.Arsenic trioxide (AsaC^) is the major effective component of Arsenicum sublimatum, one of the traditional Chinese medicine. Arsenic has been used as therapy and as a drug since ancient times. However, because of its side effects, it was not widely used in the clinic. It was believed that arsenic compounds were highly poisonous after acute exposure and carcinogenic following chronic exposure. Moreover, arsenic trioxide could result in chromosome abnormalities, sister chromatic exchange, DNA protein ligation and DNA strand degradation in mammalian cells. In 1971, Harbin Medical University firstly used As2C>3 in the treatment of acute promyelocytic leukemia (APL) with good results and few side effects, providing a new method for therapy. Results of treatment of acute promyelocytic leukemia (APL) with the trioxide form of arsenic were published in the 1990's, with complete remission rates of 65%-84% and a survival at 10 years of 28%. Toxicity was mild in these reports. Recent reports in the US confirmed the effectiveness of arsenic in APL, as well as the mild toxicity.The mechanism of action of Trisenox is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human APL cells in vitro Arsenic trioxide also causes damage or degradation of the fusion protein PML-RAR alpha. Cell apoptosis, which involves theIIIbiologic regulation of the numbers and vital activity of cells, is an important metabolic process in both normal cells and tumor cells. Delayed process of cell apoptosis will probably lead to a disturbance of metabolism, and occurrence and development of neoplasms. Song et al have proved the relationship between apoptosis delay and tumor development through inhibition of cell apoptosis induced by tumor promoter. Thus, induction of cell apoptosis could be a new strategic measure against tumor . Up to now, there is little research at home or abroad about the effects of As2Oj on K562 cell line. Here we report inducing apoptosis with As23 at different concentrations. Cells were stained with Wright s and AO/EB staining. Morphological changes of apoptosis were observed with invert fluorescence microscope. Cell proliferation was determined by MTT assay. DNA ladder and cell cycle were examined by DNA agarose gel electrophoresis and PI fluorescence flow cytometry (FCM), respectively. K562 cells treated with As2C>3 at different concentrations were examined for Bcl-2 and P53 protein expression with immunohistochemical staining examination. As2O3 i...
Keywords/Search Tags:arsenic trioxide, apoptosis, leukemia, myeloid, K562 cell line.
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