氯硝柳胺联合顺铂对裸鼠肾上腺皮质癌移植瘤的抑制作用

Inhibitory effect of combined niclosamide and cisplatin on adrenocortical carcinoma xenografts in nude mice

目的:研究氯硝柳胺联合低剂量顺铂对裸鼠肾上腺皮质癌移植瘤的抑制作用,并探讨其机制。方法:建立SW-13细胞裸鼠移植瘤模型,设对照组、氯硝柳胺组、顺铂组、联合用药组,比较各组终末肿瘤体积、瘤重、生化指标。TUNEL检测移植瘤组织的细胞凋亡率,免疫组织化学法和Western blot检测移植瘤组织Bcl-2、caspase-3的表达。结果:联合用药组的终末肿瘤体积、瘤重低于氯硝柳胺组、顺铂组(均P<0.001);顺铂组、联合用药组的白细胞低于对照组(均P<0.001),顺铂组与联合用药组比较差异无统计学意义(P=0.29);顺铂组、联合用药组的肌酐、谷丙转氨酶高于对照组(均P<0.001),顺铂组与联合用药组的肌酐、谷丙转氨酶比较差异无统计学意义(均P>0.05)。TUNEL检测显示联合用药组的细胞凋亡率高于氯硝柳胺组(P=0.004)、顺铂组(P=0.005),免疫组织化学法、Western blot检测显示联合用药组中Bcl-2表达较氯硝柳胺组、顺铂组降低(均P<0.001),caspase-3的表达升高(均P<0.001)。结论:氯硝柳胺能够增强低剂量顺铂对肾上腺皮质癌生长的抑制作用且不增加毒副作用,可能与影响Bcl-2、caspase-3表达促进肿瘤细胞凋亡相关。

Objective： To examine the inhibitory effect and mechanism of niclosamide combined with low-dose cisplatin on adrenocor- tical carcinoma xenografts in nude mice. Methods： A SW-13 cell transplanted tumor model was first established in nude mice. The nude mice were then divided into the control group, nidosamide group, cisplatin group, and combined drug group. The groups were compared in terms of tumor body volume, tumor weight, and biochemical index. The cell apoptosis rate of the transplanted tumor tis- sue was detected by TUNEL assay, while Bcl-2 and caspase-3 protein expression in the transplanted tumor tissue was detected by im- munohistochemistry and Western blot. Results： The terminal tumor volume and weight of the combined drug group were lower than those of the niclosamide and cisplatin groups （all P〈0.001）. The white blood cell count of the cisplatin and combined drug groups were lower than that of the control group （all P〈0.00I}. Meanwhile, no difference was observed between the cisplatin and combined drug groups （P=0.29）. The creatinine and glutamic pyruvic transaminase of the cisplatin and combined drug groups were higher than those of the control group （all P〈0.001）, whereas no significant difference was observed in the levels of creatinine and alanine aminotransfer- ase between cisplatin and combined drug groups （all P〉0,05）. TUNEL test results showed that the cell apoptotic rate of the combined drug group was higher than that of the niclosamJde group （P=0.004） and cisplatin group （P=O.O05）. Immunohistochemistry and West- ern blot test results showed that Bcl-2 expression in the combined drug group was lower than those of the niclosamide and cisplatin groups （all P〈0.001）, while caspase-3 expression in the combined drug group was the highest among those of other groups （all P〈 0.001）. Conclusion： Niclosamide can enhance the inhibitory effect of low-close cisplatin on the growth of adrenocortical carcinoma and has no additional side effects. This enhancement is probably related to the influence of niclosamide on Bcl-2 and caspase-3 expres- sion levels. Niclosamide promotes the apoptosis of the tumor cells by influencing Bcl-2 and caspase-3 exoression.