Effect of paclitaxel, epirubicin and cyclophosphamide used for breast cancer chemotherapy on cognition function of mice

doi:10.3877/cma.j.issn.1674-0807.2016.01.005

Abstract

Abstract:

Objective

To explore the effects of paclitaxel, epirubicin and cyclophosphamide, which are widely used in breast cancer chemotherapy, on the cognition function of mice.

Methods

Totally 80 Balb/c mice were randomized into four groups, 20 mice in each group. The mice in 3 experimental groups were intraperitoneally injected with paclitaxel (30 mg/kg), epirubicin (10 mg/kg), or cyclophosphamide alone(200 mg/kg) respectively. The mice in control group were injected with isovolumic saline. At 4 weeks after injection, all groups were given Morris water maze test, including place navigation and spatial probe test, to record the time the mice spent on underwater platform (escape latency), the ratio of time in every quadrant to total swimming time and the times of crossing the platforma. The escape latencies of mice were compared among groups using repeated measurement analysis of variance, the ratio of time in every quadrant to total swimming time was compared using univariate analysis of variance and the times of crossing the platform among groups were compared using Kruskal-Wallis rank sum test.

Results

In place navigation test, the escape latencies at 5 time points (on days 1,2,3,4,5 after injection) in four groups were decreased with training time, which showed a trend of decline (F=11.25, P=0.001). There was no statistically significant difference in escape latency between paclitaxel/ epirubicin/cyclophosphamide-treated group and control group, while escape latencies were significantly different at 5 time points (comparison between groups: F=1.23, P=0.251;comparison at different time points: F=5.94, P ＜0.001; interaction between grouping and different time points: F=0.77, P=0.676). In spatial probe test, the ratio of time spent in every quadrant to the total swimming time in 4 groups presented a significant difference (F=3.26, P=0.027); it was significantly lower in cyclophosphamide-treated group than that in control group (13.6%±8.9% vs 23.9%±13.9%;t=- 3.05,P=0.009). The difference was not statistically significant between experimental groups and control group in the times of crossing the platform on the sixth day after injection(χ² = 1.86,P = 0.602).

Conclusions

Cyclophosphamide can affect the memory maintenance of mice. There is a possibility that chemotherapy medication can affect the ability of spatial cognition and learning in mice.

Key words: Breast neoplasms, Drug therapy, Maze learning, Cognitive disorders

Wanru Yao, Jian Ren, Jiaqi He, Haichen Sun, Shuang Liu, Yue Zhao, Bin Luo. Effect of paclitaxel, epirubicin and cyclophosphamide used for breast cancer chemotherapy on cognition function of mice[J]. Chinese Journal of Breast Disease(Electronic Edition), 2016, 10(01): 20-24.

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Figures/Tables 2

组别	只数	逃避潜伏期(s, $\overset{ˉ}{x}$ ±s)
组别	只数	第1天	第2天	第3天	第4天	第5天
紫杉醇组	20	48.9±11.0	48.2±12.3	51.6±9.7	46.3±12.2	41.2±13.6
表柔比星组	20	42.8±12.0	39.0±12.6	41.7±13.8	37.4±6.2	33.9±14.6
环磷酰胺组	20	45.1±10.8	47.3±11.3	47.3±14.4	41.9±14.5	43.8±13.8
对照组	20	45.1±12.7	37.9±11.6	40.1±12.4	36.9±13.7	37.9±13.8

组别	只数	逃避潜伏期(s, $\overset{ˉ}{x}$ ±s)
组别	只数	第1天	第2天	第3天	第4天	第5天
紫杉醇组	20	48.9±11.0	48.2±12.3	51.6±9.7	46.3±12.2	41.2±13.6
表柔比星组	20	42.8±12.0	39.0±12.6	41.7±13.8	37.4±6.2	33.9±14.6
环磷酰胺组	20	45.1±10.8	47.3±11.3	47.3±14.4	41.9±14.5	43.8±13.8
对照组	20	45.1±12.7	37.9±11.6	40.1±12.4	36.9±13.7	37.9±13.8

组别	只数	目标象限时间比率(%, $\overset{ˉ}{x}$ ±s)	穿越平台次数[M(P₂₅～P₇₅)]
紫杉醇组	19	20.6±8.1	1(0～3)
表柔比星组	10	20.5±9.5	2(1～4)
环磷酰胺组	19	13.6±8.9^a	1(0～3)
对照组	20	23.9±13.9	1(0～3)
检验值		F=3.26	χ²=1.86
P值		0.027	0.602

组别	只数	目标象限时间比率(%, $\overset{ˉ}{x}$ ±s)	穿越平台次数[M(P₂₅～P₇₅)]
紫杉醇组	19	20.6±8.1	1(0～3)
表柔比星组	10	20.5±9.5	2(1～4)
环磷酰胺组	19	13.6±8.9^a	1(0～3)
对照组	20	23.9±13.9	1(0～3)
检验值		F=3.26	χ²=1.86
P值		0.027	0.602

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