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Aim: To study the effect of staurosporine (ST) on the cell cycle of human gastric cancer cell lines MGC803 and SGC7901., Methods: Cell proliferation was evaluated by trypan blue dye exclusion method. Apoptotic morphology was observed under a transmission electron microscope. Changes of cell cycle and apoptotic peaks of cells were determined by flow cytometry. Expression of p21WAF1 gene was examined using immunohistochemistry and RT-PCR., Results: The growth of MGC803 and SGC7901 cells was inhibited by ST. The inhibitory concentrations against 50% cells (IC50) at 24 h and 48 h were 54 ng/ml and 23 ng/ml for MGC803, and 61 ng/ml and 37 ng/ml for SGC7901. Typical apoptotic bodies and apoptotic peaks were observed 24 h after cells were treated with ST at a concentration of 200 ng/ml. The percentage of cells at G0/G1 phase was decreased and that of cells at G2/M was increased significantly in the group treated with ST at the concentrations of 40 ng/ml, 60 ng/ml, 100 ng/ml for 24 h, compared with the control group (P<0.01). The expression levels of p21WAF1 gene in both MGC803 and SGC7901 cells were markedly up-regulated after treatment with ST., Conclusion: ST can cause arrest of gastric cancer cells at G2/M phase, which may be one of the mechanisms that inhibit cell proliferation and cause apoptosis in these cells. Effect of ST on cells at G2/M phase may be attributed to the up-regulation of p21WAF1 gene.

Background & Objective: Protein kinase C (PKC) has been considered to be a potentially suitable target for anticancer therapy. This study was designed to investigate the effect of PKC inhibitor staurosporine (ST) on the inhibition of proliferation, the induction of apoptosis, and the change of cell cycle in human gastric cancer cell lines MGC-803 and SGC-7901., Methods: The inhibition rates of cell proliferation were evaluated by trypan blue exclusion. The apoptotic bodies were observed under light microscope and electron microscope. The apoptotic peaks of the cells and the changes of cell cycle were analyzed using flow cytometry., Results: ST inhibited cell growth of MGC-803, IC(50) of 24 hours was 54 ng/ml and IC(50) of 48 hours was 23 ng/ml. ST inhibited cell growth of SGC-7901, IC(50) of 24 hours was 61 ng/ml and IC(50) of 48 hours was 37 ng/ml. MGC-803 cells were treated by ST at the concentrations of 40, 60, and 100 ng/ml for 24 hours, the percentages of G(0)/G(1) phage were 23.6+/-1.8%, 11.6+/-0.7%, and 3.3+/-0.2%, respectively (54.3+/-3.1% in control group); the percentages of G(2)/M phage were 22.6+/-4.0%, 35.5+/-0.4%, and 36.8+/-5.5%, respectively (13.5+/-0.2 in control group). SGC-7901 cells were treated by ST at the concentrations of 40, 60, and 100 ng/ml for 24 hours, the percentages of G(0)/G(1) phage were 27.1+/-1.4%, 17.0+/-3.4%, 13.7+/-0.7%, respectively (52.5+/-4.4% in control group); the percentages of G(2)/M were 21.9+/-2.6%, 39.5+/-4.9%, and 38.4+/-3.1%, respectively (13.5+/-2.2% in control roup). Compared with the control group, the percentages of G(0)/G(1) phage of two cell lines decreased and that of G(2)/M cells increased significantly in the ST treated group(P< 0.01). Treated by ST at the concentration of 200 ng/ml, the apoptotic peaks and typical apoptotic bodies were observed., Conclusion: ST significantly inhibits the proliferation and induces apoptosis of MGC-803 cells and SGC-7901 cells; ST induces G(2)/M phase arrest.

Background/Aims Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a newly identified biological agent has shown promising antitumor effects in a wide range of cancers. However, gastric cancer cells are less sensitive than other cancer cells to TRAIL-induced apoptosis.Here, we combined TRAIL with bortezomib, a proteasomal inhibitor to induce apoptosis in three gastric cancer cell lines.Methods After the cells were treated with TRAIL and/or bortezomib, the cell viability, apoptosis and cell cycle distribution were examined. The levels of death receptors and the mitochondrial membrane potential were also detected. The expression of apoptosis-associated proteins was determined by Western blot.Results Bortezomib at low concentration significantly(P<0.05) enhanced the cytotoxic effect of TRAIL by enhancing apoptosis as well as cell cycle arrest at G2/M phase. The enhancement of efficiency of TRAIL by bortezomib involved up-regulation of death receptor 4 and 5, as well as reduction of the mitochondrial membrane potential. Further study showed that combined treatment with TRAIL and bortezomib down-regulated anti-apoptotic protein cIAP-1, and over expression of cIAP-1 significantly(P\0.05) reduced the synergistic effect between TRAIL and bortezomib.Conclusions Bortezomib synergizes TRAIL-induced apoptosis in human gastric cancer cells. The synergistic effect between these two drugs is associated with up-regulation of death receptors and down-regulation of cIAP-1.The combination of TRAIL and bortezomib might be an effective regimen for the treatment of advanced gastric cancer. [ABSTRACT FROM AUTHOR]