摘要
目的:评价奥沙利铂(Oxaliplatin,L-OHP)对人胃癌的疗效,探讨其治疗胃癌的作用机制。方法:Ⅳ期胃癌患者22例接受包含L-OHP的联合化疗方案(L-OHP 85 mg/m^2,静脉点滴,1h,第1d;四氢叶酸钙200 mg/m^2,静脉点滴,1h,第1-5 d;5-FU 300mg/m^2,静脉注射,第1-2d,5-FU,持续静脉点滴,48h;2wk1疗程)4-6(平均4.6)个疗程.观察有效率,无进展生存时间(progression-free survival,PFS),总体生存时间及毒副作用。体外培养人中分化胃癌细胞株SGC-7901,应用MTT法检测L-OHP对细胞生长的抑制作用,并计算50％抑制浓度(IC_(50));将不同浓度梯度的L-OHP与细胞株作用后,应用流式细胞仪(ANEXIN-V标记)及TUNEL检测细胞凋亡情况。应用RT-PCR检测caspase-3m-RNA的表达。结果:有效(完全有效及部分有效)9例(40.9％)。平均PFS4.2mo,总体生存时间7.2mo。蓄积性神经毒性(全部为Ⅰ-Ⅱ级),呕吐及腹泻(1例Ⅲ级腹泻),骨髓抑制发生率分别为93.5％,20％,32.9％.浓度为1mmol/L的L—OHP与细胞株作用30min,流式细胞仪即可检测出细胞凋亡水平升高,但无统计学差异(P>0.05),1mmol/L作用2d,流式细胞仪及TUNEL均可检测到细胞凋亡水平显著性升高(P<0.05)。L-OHP作用后的细胞caspase-3 m-RNA表达升高,并与药物诱导的凋亡相关。结论:L-OHP治疗进展期胃癌安全有效.L-OHP在体外可明显抑制胃癌细胞株SGC-7901的生长,诱导细胞caspase-3m-RNA表达及凋亡。
AIM: To evaluate the therapeutic effect of oxaliplatin on human gastric carcinoma and to explore the mechanisms. METHODS: 22 cases of stage Ⅳ gastric carcinoma pa- tients 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 IC_(50) 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 neu- rotoxicity (all grade Ⅰ - Ⅱ), 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 0xaliplatin for 2 days. Caspase-3 mRNA expression was elevated in oxaliplatin treated cells and correlated with agoptosis 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
出处
《世界华人消化杂志》
CAS
2003年第10期1535-1539,共5页
World Chinese Journal of Digestology
