Inhibitory effect of combined niclosamide and cisplatin on adrenocortical carcinoma xenografts in nude mice
10.3969/j.issn.1000-8179.2017.07.482
- VernacularTitle: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
- Author:
Minjie WANG
;
Weilie HU
;
Wei WANG
;
Yi ZHU
;
Xu ZHAO
- Keywords:
niclosamide;
cisplatin;
SW-13;
Bcl-2;
caspase-3
- From:
Chinese Journal of Clinical Oncology
2017;44(7):306-310
- CountryChina
- Language:Chinese
-
Abstract:
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, niclosamide 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<0.001). 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 niclosamide group (P=0.004) and cisplatin group (P=0.005). 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-dose 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 expression.