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1.
Chinese Medical Journal ; (24): 100-104, 2005.
Article in English | WPRIM | ID: wpr-257316

ABSTRACT

<p><b>BACKGROUND</b>Arsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics.</p><p><b>METHODS</b>K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis.</p><p><b>RESULTS</b>As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells.</p><p><b>CONCLUSIONS</b>As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Arsenicals , Pharmacology , Dose-Response Relationship, Drug , K562 Cells , Nuclear Matrix-Associated Proteins , Oxides , Pharmacology , Proteomics
2.
Chinese Journal of Oncology ; (12): 230-233, 2003.
Article in Chinese | WPRIM | ID: wpr-347455

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the correlation of bcl-2 and Bax protein with nuclear matrix in glioblastoma cell line U87 as well as the effect of EGFR-cDNA transfection on the expression of bcl-2 and Bax in U87 cells.</p><p><b>METHODS</b>The correlation of bcl-2 and Bax protein with nuclear matrix in glioblastoma cell line U87 was studied by confocal microscopy and Western blot. The expression of bcl-2 and Bax in EGFR-cDNA transfected and untransfected glioblastoma cell lines was studied by Western blot.</p><p><b>RESULTS</b>Confocal microscopic images showed that bcl-2 protein was localized in the periphery of the nuclear matrix and Bax in the nuclear matrix. A 26 kDa bcl-2 band and a specific band of Bax at about 66 000 were detected in nuclear matrix proteins by western blot. The expression of bcl-2 was lower but that of Bax was higher in EGFR-cDNA transfected cells than the control.</p><p><b>CONCLUSION</b>Bcl-2 and Bax, being nuclear matrix associated proteins, are probably involved in the EGFR-cDNA induced malignant conversion of glioblastoma cells by introducing EGFR cDNA into the tumor cells.</p>


Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Glioblastoma , Pathology , Nuclear Matrix , Chemistry , Proto-Oncogene Proteins c-bcl-2 , Physiology , ErbB Receptors , Genetics , Physiology , Transfection , bcl-2-Associated X Protein , Physiology
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