| Background Arsenic at low doses has been used as an ancient drug in Traditional Chinese Medicine for almost one thousand years,and for tumor chemotherapy for centuries. But as a extreme poison, arsenic could induce many cytogenetical changes,such as chromosome loss, breakage and sister chromatid exchange and so on. So for a long period,the medical values of arsenic were covered with its toxicities and side effects. Recent reports in China showed that arsenic trioxide (As203) is a very effective treatment for patients with acute promyelocytic leukemia (APL),the following studies demostrated that the mainly mechanism is inducing APL cell apoptosis. another surprising finding from the same group that surprised everybody with ATRA? said Raymond Warrell in the journal Science.Many domestic and foreign scholars are very interested in the antitumor effect of arsenic.However,the researches of the effects of arsenite on the solid tumors have just begun and the exact antitumor mechanisms are not well known.Therefor,in this article, we studied the the biological effects of arsenic trioxide on human gastric carcinoma cell line SGC-7901 in vitro, in order to provide a theoretical evidence for searching an new agent for the treatment of gastric carcinoma in the future. Obsjectives 1 . To study the biological effects of inhibiting proliferation and iuducing apoptosis by arsenic trioxide on human gastric carcinoma SGC-790 1 cell in vifro. 2 . To investigate the potential mechanisms of the effects of arsenic trioxide on human gastric carcinoma SGC-7901 cell. Methods 1 Cell culture:The human gastric carcinoma SGC-7901 cell line was cultured in RPMI- 1640 medium supplemented with 15% heat- inactivated fetal calf serum at 370C ,5% CO2 in air. 2 After treated with 1 8 jt molIL As203 for 12 8 hours, the effect of As203 on the proliferation ofSGC-7901 cells was measured By means of MIT reduction assay. 3 Morphological changes were observed under the light and electron microscopy. 4.. Apoptotic index (Al) was detected by Flow Cytometry (FCM7) and terminal deoxynucleotidyl transferase mediated dUTP nick end fabling (TUNEL) method. 5 The cell cycle was analysed by FCM and the light microscopy. 6 The expressions of proliferating cell nuclear antigen (PCNA), Bcl-2,Bax,c-Myc and P53 were detected by immunohistochemistry. 7 The expressions of Apo2.7 and Caspase-3 were determined by Flow Cytometiy. 8 Dithiothreitol (DTT) was used as a disulfide bond-reducing agent and the effect of DTT on arsenic trioxide-induced SGC-7901 cell apoptosis was investigated. 9 The results of TUNEL and immunohistochemistry were analysed by Computer Image Analysis System NYD- 1000. Results 1 As2O3 could significantly inhibit the proliferation of 8(1(2-7901 cells,especially at the concentration of more than 2 祆 mo ilL, and the inhibtory effect was dose-and-time-dependent. 2 . The typical apoptotic morphology and the degeneration of mitochondrial were observed after treatment with As203. 3-. After treated with 4 8 t mol/L As203 for 12,24 and 48 hours,the histogramic analysis of DNA contents revealed the appearance of hypodiploid DNA peak immerged before (11 phase.And the same time, As203 could also induce a G2/M phase arrest to the different degrees in this cell line with the G0/Gl phase proportions down-regulated. 4-. The apoptotic index of 5(1(2-7901 cell measured by... |
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