Induction of apoptosis by arsenic trioxide and hydroxycamptothecin in gastric cancer cells in vitro

AIM To study the effects of arsenic trioxide and HCPT on different degrees of differentiated gastric cancer cells(SGC-7901,MKN-45,MKN-28)with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS The cytotoxicity of As_2O_3 and HCPT on gastric cancer cells was determined by MTT assay.Morphologic changes of apoptosis of gastric cancer cells were observed by light microscopy and transmission electron microscopy. Apoptosis and cell cycle changes of gastric cancer cells induced by HCPT and As_2O_3 were investigated by TUNEL method and flow cytometry. RESULTS As_2O_3 and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells.The IC_(50)of As_2O_3 on well differentiated gastric cancer cell MKN-28,moderately differentiated gastric cancer cell SGC-7901,and poorly differentiated gastric cancer cell MKN-28 were 8.91 μmol/L,10.57 μmol/L,and 11.65 μmol/L,respectively.The IC_(50) of HCPT on MKN-28,SGC-7901,and MKN-45 were 9.35 mg/L,10.21 mg/L,and 12.63 mg/L respectively after 48 h treatment.After 12 h of exposure to both drugs,gastric cancer cells exhibited morphologic features of apoptosis, including cell shrinkage,nuclear condensation, and formation of apoptotic bodies.A typical subdiploid peak before G_0/G_1 phase was observed by flow cytometry.The apoptotic rates of SGC- 7901,MKN-45,and MKN-28 were 13.84%, 22.52%,and 9.68%,respectively after 48 h exposure to 10 μmol/L As_2O_3.The apoptotic rates of SGC-7901,MKN-45,and MKN-28 were 21.88%, 12.35%,and 30.26%,respectively after 48 h exposure to 10 mg/L HCPT.The apoptotic indice were 7%-15% as assessed by TUNEL method. The effect of As_2O_3 on SGC-7901 showed remarkable cell cycle specificity,which induced cell death in G_1 phase,and blocked G_2/M phase. HCPT also showed a remarkable cell cycle specificity,by inducing cell death and apoptosis in G_1 phase and arrest of proliferation at S phase. CONCLUSION As_2O_3 and HCPT exhibit significant cytotoxicity on gastric cancer cells by induction of apoptosis.As_2O_3 and HCPT might have a promising prospect in the treatment of gastric cancer,which needs to be further studied.