AIM:To evaluate the therapeutic effectiveness of oxaliplatinon human gastric carcinoma and to explore its mechanisms.METHODS:Twenty-two cases of stage IV gastric carcinomareceived 4-6(mean 4.6)cycles of first line combinedchemotherapy with oxaliplatin(oxaliplatin 85 mg/m~2,iv,gtt,1 h,d 1;leukovorin 200 mg/m~2,iv,gtt,1 h,d 1 and d 2;5-FU 300 mg/m~2,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 lineSGC-7901 was detected and IC_(50) was calculated by MTT.Transmission electron microscopy,flow cytometry andTUNEL were performed to evaluate the apoptosis of cellline induced by the drug.The expression of Caspase-3m-RNA was detected by RT-PCR.AC-DEVD-CHO,aCaspase-3 specific inhibitor,was used to elucidate the roleof activated Caspase-3 in the process of apoptosis inducedby oxaliplatin.RESULTS:Total response(complete and partial)occurredin 9(40.9%) patients.Mean PFS was 4.2 mo and meantotal survival time was 7.2 mo.Cumulative neurotoxicity(all grade Ⅰ-Ⅱ),vomiting and diarrhea,myelosuppressionappeared in 93.5%,20%,32.9% patients,respectively.IC_(50) was calculated to be 0.71 mg/L by MTT assay.A maximalinhibitory rate reached 85.3%.Apoptosis index was elevatedafter incubated with 1 mmol/L oxaliplatin for 30 min,butwithout statistic significance(P>0.05).However it couldbe detected at a much higher degree both by flowcytometryand by TUNEL with a statistical significance(68.47±7.92%and 8.23±2.67%,respectively,P<0.05)after incubated with1 mmol/L oxaliplatin for 2 d.By means of RT-PCR,we detectedan enhancement of Caspase-3 m-RNA expression inducedby oxaliplatin which was also in positive correlation withthe apoptotic level.AC-DEVD-CHO,a Caspase-3 specificinhibitor,could significantly inhibit and delay apoptosisinduced by oxaliplatin.CONCLUSION:Oxaliplatin is effective and well-toleratedin patients with advanced gastric carcinoma.Oxaliplatincould significantly inhibit the growth of human gastric cell lineSGC-7901.The induction of Caspase-3 m-RNA expression,activation of Caspase-3 and promotion of apoptosis maybe some of the therapeutic mechanisms of oxaliplatin ongastric carcinoma.Annexin-V-fluorescein labeling flowcytometry is much more sensitive than TUNEL in detecting early stage apoptosis. 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 reproduced 4-6 (mean 4.6) cycles of first line combined chemotherapy with oxaliplatin (oxaliplatin 85 mg / m ~ 2, iv, gtt, 1 h, d 1; leukovorin 200 mg / m 2, iv, gtt, 1 h, d 1 and d 2; 5-FU 300 mg / m 2, 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 as.The inhibitory effect of oxaliplatin on human gastric cell lineSGC-7901 was detected and IC_ (50) was calculated by MTT. Transmission electron microscopy, flow cytometry and TUNEL were performed to evaluate the apoptosis of cellline induced by the drug. The expression of Caspase-3m-RNA was detected by RT-PCR. AC-DEVD-CHO, aCaspase-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 meaningotal survival time was 7.2 mo.Cumulative neurotoxicity (all grade Ⅰ-Ⅱ), vomiting and diarrhea, myelosuppression in 93.5%, 20%, 32.9% patients, respectively.IC_ (50) was calculated to be 0.71 mg / L by MTT assay. A maximal inhibition rate reached 85.3% .Apoptosis index was elevated after incubation with 1 mmol / L oxaliplatin for 30 min, withwithout statistic significance (P> 0.05) at a much higher degree both by flow cytometry and by TUNEL with a statistical significance (68.47 ± 7.92% and 8.23 ​​± 2.67%, respectively, P <0.05) after incubation with 1 mmol / L oxaliplatin for 2 d. 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 -toleratedin patients with advanced gastoxaliplatincould 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 maybe some of the therapeutic mechanisms of oxaliplatin ongastric carcinoma. -fluorescein labeling flowcytometry is much more sensitive than TUNEL in detecting early stage apoptosis.