Effects of allitridi on cell cycle arrest of human gastric cancer cells

AIM: To determine the effect of allitridi on cell cycle of human gastric cancer (HGC) cell lines MGC803 and SGC7901 and its possible mechanism. METHODS: Trypan blue dye exclusion was used to evaluate the proliferation, inhibition of cells and damages of these cells were detected with electron microscope. Flow cytometry and cell mitotic index were used to analyze the change of cell cycle, immunohistochemistry, and RTPCR was used to examine expression of the p21(WAF1) gene. RESULTS: MGC803 cell growth was inhibited by allitridi with 24 h IC(50) being 6.4 mu g/mL. SGC7901 cell growth was also inhibited by allitridi with 24 h IC(50) being 7.3 mu g/mL. After being treated with allitridi at the concentration of 12 mu g/mL for 24 h, cells were found to have direct cytotoxic effects, including broken cellular membrane, swollen and vesiculated mitochondria and rough endoplasmic reticula, and mass lipid droplet. When cells were treated with allitridi at the concentration of 3, 6, and 9 mu g/mL for 24 h, the percentage of G(0)/G(1) phase cells was decreased and that of G(2)/M phase cells was significantly increased (P = 0.002) compared with those in the group. When cells were treated with allitridi at the concentration of 6 mu g/mL, cell mitotic index was much higher (P = 0.003) than that of control group, indicating that allitridi could cause gastric cancer cell arrest in M phase. Besides, the expression levels of p21(WAF1) gene of MGC803 cells and p21(WAF1) gene of SGC7901 cells were remarkably upregulated after treatment. CONCLUSION: Allitridi can cause gastric cancer cell arrest in M phase, and this may be one of the mechanisms for inhibiting cell proliferation. Effect of allitridi on cells in M phase may be associated with the upregulation of p21(WAF1) genes. This study provides experimental data for clinical use of allitridi in the treatment of gastric carcinoma. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.