药物敏感试验指导小鼠胃癌化疗对凋亡及P53基因的影响

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,了解其疗效以及对移植瘤凋亡及P53基因的影响.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,检测凋亡及P53基因的表达.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,其抑瘤率高,凋亡率高,P53基因的表达下降,与对照组比较有显著性差异;最不敏感的ADM化疗组抑瘤率低,凋亡率低,P53基因的表达高于对照组(P＜0.05).再对已行化疗的胃癌细胞筛选最敏感药物为DDP,最不敏感药物为用MMC,对第二代荷瘤小鼠进行化疗,发现DDP组抑瘤率高,凋亡率高,P53基因的表达较对照组低(P＜0.05);MMC组抑瘤率低,凋亡率低, P53蛋白表达高,与对照组比较无显著性差异.而继用5-FU和ADM化疗对第二代荷瘤小鼠进行化疗,抑瘤率低,凋亡率低,P53基因的表达高,与对照组比较无显著性差异.结论:药敏试验、凋亡及P53基因的检测可作为化疗药物的选择及判断预后的指标.

Effect of chemotherapy under the instruction of drug sensitivity test on apoptosis and P53 gene in the mice with gastric cancer

AIM: To study the effect of chemotherapy under the instruction of drug sensitivity test on apoptosis and P53 gene in the mice with gastric cancer. METHODS: Chemosensitivity of mouse gastric cancer cells to 6 anticancer drugs was investigated using MTT, and the 6 anticancer drugs were applied to mice with implanted tumor.The volume of implanted tumor and tumor inhibition rate were observed, and the cell apoptosis and the expression of P53 were detected. RESULTS: The most sensitive drug was 5-FU; the tumor inhibition rate and apoptosis rate of 5-FU group were higher, and the expression of P53 was lower than those of control group(P<0.05).The most insensitive drug was adriamycin(ADM); the tumor inhibition rate and apoptosis rate were lower, and P53 expression of ADM group was increased as compared with that of control group(P<0.05).The most sensitive drug was cisplatin(DDP) for mice with gastric cancer which had been treated by 5-FU, and the most insensitive drug was mitomycin (MMC) for mice with gastric cancer which had been treated by ADM; the tumor inhibition rate and apoptosis rate of DDP group were higher, and P53 expression was lower than those of control group(P<0.05), and the tumor inhibition rate and apoptosis rate of MMC group were lower, and P53 expression had no significant difference as compared with those of control group. However, the tumor inhibition rate and apoptosis rate of 5-FU group and ADM group in the second-generation mice with implanted tumor were lower, and P53 expression had no significant difference as compared with those of control group. CONCLUSION: Scientific individual chemotherapy should be performed under the instruction of drug sensitivity test and drug resistance gene detection. In vitro drug sensitivity test, apoptosis and P53 detection can guide the clinical use of anticancer drugs.