药物敏感试验指导小鼠多次传代胃癌化疗的疗效及耐药基因观察

Drug sensitivity test and drug-resistance gene assessment for chemotherapy planning for tumors derived from high-passage mouse gastric cancer cells:therapeutic effect observation in mice

目的通过应用药敏试验筛选化疗药物对多次传代的荷瘤鼠进行化疗,了解其疗效及耐药基因的表达。方法用MTT法检测小鼠胃癌细胞对6种化疗药物的敏感性,对荷瘤鼠进行化疗,观察化疗后移植瘤的体积、抑瘤率,检测多药耐药基因1(MDR1)的表达。结果用MTT法筛选最敏感的化疗药5-FU对第一代荷瘤小鼠进行化疗,其抑瘤率显著高于对照组,但MDR1的表达与对照组无显著性差异;筛选的最不敏感的阿霉素化疗组抑瘤率低,MDR1的表达与对照组比较无显著性差异。再对已行化疗的胃癌细胞筛选最敏感药物为顺铂,最不敏感药物为丝裂霉素。对第2代荷瘤小鼠进行化疗,发现顺铂组抑瘤率高,但MDR1的表达与对照组无显著性差异;丝裂霉素组抑瘤率低,MDR1表达高,与对照组比较有显著性差异。继而用5-FU和阿霉素对第2代荷瘤小鼠进行化疗,抑瘤率低,MDR1表达与对照组比较无显著性差异。结论应根据药敏试验和耐药基因来实施科学的、药物适配的个体化化疗方案。

Objective To study the effect of chemotherapy with drugs selected according to drug sensitivity test and drug- resistance gene assessment in mice bearing tumors derived from high-passage gastric cancer cells. Methods Chemosensitivity of the mouse gastric cancer cells to 6 chemotherapeutic drugs was investigated using MTT assay before the 6 drugs were applied in mice with implanted tumors. The implanted tumor volume and tumor inhibition rate were observed, and the expression of the multidrug resistance-1 （MDR1） gene was detected. Results 5-FU, the most sensitive among the 6 drugs, resulted in significantly higher tumor inhibition rates in comparison with the control group, but did not significant affect MDR1 expression. Adriamycin （ADM） had the lowest sensitivity with low tumor inhibition rates and no significant effect on MDR1 expression. Cisplatin （DDP） was identified as the most sensitive drug for mouse gastric cancer with previous 5-FU exposure, and Mitomycin （MMC） was the most insensitive drug for mouse gastric cancer with previous ADM treatment. In mice bearing tumors of the second-passage cells, DDP showed high tumor inhibition rate but scarcely affected MDR1 expression; MMC resulted in low tumor inhibition rate and high MDR1 expression. Application of 5-FU and ADM in these tumor-bearing mice of the second-passage cancer cells resulted in rather low tumor inhibition rates without significant alterations in MDRI expression as compared with the control group. Conclusion Appropriate individualized chemotherapy should be implemented in full consideration of the results of drug sensitivity test and drug-resistance gene assessment.