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AIM: To evaluate the therapeutic effectiveness of oxaliplatin on human gastric carcinoma and to explore its mechanisms.METHODS:Twenty-two cases of stage Ⅳ gastric carcinoma received 4-6 (mean 4.6) cycles of first line combined chemotherapy with oxaliplatin (oxaliplatin 85 mg/m2,iv,gtt,1 h,d 1;leukovorin 200 mg/m2,iv,gtt,1 h,d 1 and d 2;5-FU 300 mg/m2,iv,d 1 and d 2,5-FU,continuous iv,gtt,48 h;1 cycle/2 wk).Response rate,progression-free survival (PFS),total survival time,toxic side effects were evaluated.The inhibitory effect of oxaliplatin on human gastric cell line SGC-7901 was detected and IC50 was calculated by MTT.Transmission electron microscopy,flow cytometry and TUNEL were performed to evaluate the apoptosis of cell line induced by the drug.The expression of Caspase-3m-RNA was detected by RT-PCR.AC-DEVD-CHO,a Caspase-3 specific inhibitor,was used to elucidate the role of activated Caspase-3 in the process of apoptosis induced by oxaliplatin.RESULTS:Total response (complete and partial) occurred in 9 (40.9％) patients.Mean PFS was 4.2 mo and mean total survival time was 7.2 mo.Cumulative neurotoxicity (all grade Ⅰ-Ⅱ),vomiting and diarrhea,myelosuppression appeared in 93.5％,20％,32.9％ patients,respectively.IC50 was calculated to be 0.71 mg/L by MTT assay.A maximal inhibitory rate reached 85.3％.Apoptosis index was elevated after incubated with 1 mmol/L oxaliplatin for 30 min,but without statistic significance (P＞0.05).However it could be detected at a much higher degree both by fiowcytometry and by TUNEL with a statistical significance (68.47±7.92％ and 8.23±2.67％,respectively,P＜0.05) after incubated with 1 mmol/L oxaliplatin for 2 d.By means of RT-PCR,we detected an enhancement of Caspase-3 m-RNA expression induced by oxaliplatin which was also in positive correlation with the apoptotic level.AC-DEVD-CHO,a Caspase-3 specific inhibitor,could significantly inhibit and delay apoptosis induced by oxaliplatin.CONCLUSION:Oxaliplatin is effective and well-tolerated in patients with advanced gastric carcinoma.Oxaliplatin could significantly inhibit the growth of human gastric cell line SGC-7901.The induction of Caspase-3 m-RNA expression,activation of Caspase-3 and promotion of apoptosis may be some of the therapeutic mechanisms of oxaliplatin on gastric carcinoma.Annexin-V-fluorescein labeling flow cytometry is much more sensitive than TUNEL in detecting early stage apoptosis.