顺铂联合雷帕霉素、3-MA对裸鼠肺腺癌A549细胞原位移植瘤的影响

Influence on combined Rapamycin or 3-MA with cisplatin in orthotopically implanted tumors in nude mice

目的探讨顺铂(DDP)分别联合雷帕霉素(Rapamycin,RAPA)、3-甲基腺嘌呤(3-Methyladenine,3-MA)对裸鼠肺腺癌A549细胞原位移植瘤的生长抑制作用和相关机制。方法采用RT-PCR、免疫组化SP法检测经药物作用后裸鼠移植瘤中m TOR、LC3-Ⅱ及Bax基因和蛋白水平的表达。结果 m TOR mRNA在DDP+RAPA组、DDP+3-MA组的表达量显著低于空白组和DDP组(P<0.05);LC3-ⅡmRNA在DDP+RAPA组表达量显著高于其它组(P<0.05);Bax mRNA的表达量在DDP+3-MA组的相对表达量显著高于其它组(P<0.05)。m TOR蛋白在DDP+RAPA组、DDP+3-MA组的表达强度显著低于空白组和DDP组(P<0.05);LC3-Ⅱ蛋白在DDP+RAPA组的表达显著高于其它组(P<0.05);Bax蛋白在DDP+3-MA组的表达强度显著高于其它组(P<0.05)。治疗后空白组、DDP组、DDP+RAPA组及DDP+3-MA组对裸鼠肿瘤的抑制率分别为0、36.5%、43.9%、55.0%。结论 DDP联合RAPA或3-MA均可以明显抑制肺腺癌A549细胞裸鼠移植瘤的生长,并且抑制作用均大于单独使用DDP。

Purpose To investigate the effects of Cisplatin, Cisplatin and Rapamycin （ RAPA）, Cisplatin and 3-methyladenine （ 3- MA） on orthotopically implanted tumor in nude mice. Methods The expression of mTOR, LC3-Ⅱ and Bax mRNA in nude mice transplanted tumor was examined by RT-PCR and immunohistochemical SP method. Results The expression of mTOR mRNA in DDP ＋ RAPA group and DDP ＋ 3-MA group was significantly lower than that of blank group and cisplatin group （ P 〈 0. 05 ）, that of LC3-Ⅱ mRNA in DDP ＋ RAPA group was significantly higher than other groups （ P 〈 0. 05 ）, that of Bax mRNA in DDP ＋ 3-MA group was significantly higher than that of other groups （P 〈 0. 05）, that of mTOR in DDP ＋ RAPA group and DDP ＋ 3-MA group was significantly lower than that of blank group and cisplatin group （P 〈 0. 05 ）, that of LC3- Ⅱ in DDP ＋ RAPA group was significantly higher than that of other groups （ P 〈 0. 05 ）, and that of Bax in DDP ＋ 3-MA group was significantly higher than that of other groups （P 〈 0. 05 ）. Conclusion Combined 3-MA or rapamycin with cisplatin inhibit the growing of transplantation tumor in nude mice, which effect is greater than cisplatin alone.