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 As2O3 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 As2O3 were investigated by TUNEL method and flow cytometry. RESULTS As2O3 and HCPT had remarkable cytotoxic effects on different degrees of differentiated gastric cancer cells. The IC50 of As2O3 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 mu mol/L, 10. 57 mu mol/L, and 11.65 mu mol/L, respectively. The IC50 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 mu mol/L As2O3 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 As2O3 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 As2O3 and HCPT exhibit significant cytotoxicity on gastric cancer cells by induction of apoptosis. As2O3 and HCPT might have a promising prospect in the treatment of gastric cancer, which needs to be further studied.