肌氨酰胺亚硝脲在荷神经元外单胺递质载体和DNA修复基因表达的人肺癌裸鼠中的抗肿瘤作用

Anti-tumor efficacy of 2-chloroethyl-3-sarcosinamide-1-nitrosourea in a human lung cancer xenograft model with DNA repair gene expressions

目的 探讨抗癌新药肌氨酰胺亚硝脲 (2 chloroethyl 3 sarcosinamide 1 nitrosourea ,SarCNU)在体内对DNA修复基因表达阳性肿瘤的抗肿瘤作用。方法 将人肺癌细胞株NCI H5 2 2接种于裸鼠皮下 ,制作肿瘤模型 ,观察SarCNU的抗肿瘤作用。同时 ,采用逆转录 -聚合酶链反应 (reverse transcriptionpolymerasechainreac tion ,RT PCR)测定肿瘤标本的神经元外单胺递质载体 (extraneuronalmonoaminetransporter ,EMT)和DNA修复基因六氧甲基鸟嘌呤DNA甲基转移酶 (O6 methylguanine DNAmethyltransferase ,MGMT)、核苷酸剪切修复基因ER CC1 6 (excisionrepaircross complementingrodentrepairdeficiencygene 1 6 )的表达。结果 荷瘤鼠接受SarCNU治疗后肿瘤均明显缩小 ,实验组肿瘤与对照组肿瘤大小变化 (T/C % )最佳比值为 2 3 ,肿瘤生长延缓达 5 5天 ,显示了良好的抗肿瘤作用。肿瘤细胞的EMT和DNA修复基因MGMT以及ERCC1 6的表达均为阳性。结论 在EMT阳性的肿瘤 ,即使具有DNA修复基因表达 。

Objective To clarify whether 2chloroethyl3sarcosinamide1nitrosourea (SarCNU) has an antitumor effect in DNA repair gene expressing tumors. Methods Human nonsmall cell lung cancer cell line, NCIH522, was implanted into 25 athymic mice and 6 were treated with SarCNU 120?mg/kg once a day for 5 times intraperitoneally (ip). The left ones were given normal saline. The extraneuronal monoamine transporter (EMT) expression, DNA repair gene O6methylguanineDNA methyltransferase (MGMT) and excision repair crosscomplementing rodent repair deficiency gene (ERCC16) expressions were detected in the tumor specimens by using reversetranscription polymerase chain reaction (RTPCR). Comparison of tumor size change between two groups was illustrated with T/C%.Results All the tumors were reduced in size through the treatment of SarCNU with the optimal T/C% of 23 at day 28. The tumor growth delay was 55 days, but no tumor free animals were observed. Positive EMT and DNA repair gene expression were observed in all tumor samples. Conclusion The results suggest that antitumor effect of SarCNU in EMT positive tumor is satisfactory even though the tumor exhibits DNA repair gene expression, specifically MGMT and ERCC1-6.