Clinical efficacy and mechanism of oxaliplatin in treating human gastric carcinoma

AIM: To evaluate the therapeutic effect of oxaliplatin on human gastric carcinoma and to explore the mechanisms. METHODS: 22 cases of stage gastric carcinoma patients received 4-6 (mean 4.6) cycles of first line combined chemotherapy with oxaliplatin (oxaliplatin 85 mg/m 2 , ivgtt, 1 h, d 1; leukovorin 200 mg/m 2 , iv, gtt, 1 h, d 1-5; 5-FU 300 mg/m 2 ,iv, d 1-2; 5-FU, continuously iv, gtt, 48 h; 1 cycle/2w). 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 calculated by MTT and IC50 was measured. Flow cytometry and TUNEL were applied to evaluate the apoptosis of cell line induced by the drug. The expression of caspase-3 mRNA was detected by RT-PCR. RESULTS: Total response (complete and partial) occurred in 9 (40.9 %) patients. Mean PFS was 4.2 months and mean total survival time was 7.2 months. Cumulative neurotoxicity (all grade - ), vomiting and diarrhea, myelosuppression appeared in 93.5 %, 20 %, 32.9 % of the patients, respectively. Apoptosis index was elevated after incubating with 1 mmol/L oxaliplatin for 30 min, but without statistic significance (P >0.05), but was much higher both by flowcytometry and TUNEL with statistical significance (P <0.05) after incubating with 1 mmol/L oxaliplatin for 2 days. Caspase-3 mRNA expression was elevated in oxaliplatin treated cells and correlated with apoptosis induced by the drug. CONCLUSION: Oxaliplatin is effective and well-tolerated on human advanced gastric carcinoma. Oxaliplatin could significantly inhibit the growth of human gastric cell line SGC-7901, inducing caspase-3 mRNA expression and cell apoptosis