鞣花酸对乳腺癌细胞MDA-MB-231 增殖及SDF1α/CXCR4 信号通路的影响

doi:10.3877/cma. j. issn.1674-0807.2013.06.005

目的

探讨鞣花酸对乳腺癌细胞MDA-MB-231 的增殖侵袭转移的作用。

方法

采用0(对照)、6、12 μg/ml 鞣花酸培养液分别处理乳腺癌细胞MDA-MB-231,分别于培养后24、48、72 h 计数MDA-MB-231 细胞数。细胞趋化实验观察鞣花酸对MDA-MB-231 细胞趋化运动的影响,Western Blot 观察鞣花酸对乳腺癌细胞MDA-MB-231 中SDF-1α 信号通路激活的抑制作用。数据分析采用重复测量的方差分析,两两比较采用SNK-q 分析方法。

结果

与对照组比较, 6、12 μg/ml 鞣花酸处理组在24、48、72 h 的细胞计数显著降低。重复测量的方差分析结果提示分组比较(F=4875.56,P=0.00)及三个时间点间比较(F=670.73,P=0.00)差异有统计学意义,而分组与时间有交互作用(F=122.92,P=0.00),表明鞣花酸对乳腺癌MDA-MB-231 细胞增殖有显著抑制作用。乳腺癌细胞趋化运动实验提示各组乳腺癌细胞的趋化数分别为(14.00±1.00)×10⁵/ml、(7.70±0.58)×10⁵/ml、(3.00±1.00)×10⁵/ml,差异有统计学意义(F=117.57, P=0.00)。 Western Blot 结果显示鞣花酸明显抑制CXCR4 表达及SDF1α/CXCR4 对乳腺癌细胞AKT 信号通路的激活。

结论

鞣花酸可抑制乳腺癌MDA-MB-231 细胞增殖,SDF1α/CXCR4介导的细胞趋化运动及其SDF1α/CXCR4 信号通路激活,在预防乳腺癌复发及转移中可能有潜在价值。

关键词: 鞣花酸, 乳腺肿瘤, 受体,CXCR4

Objective

To investigate the effect of ellagic acid on proliferation and invasion and metastasis of breast cancer cells MDA-MB-231.

Methods

The MDA-MB-231 cells were cultured and treated with 0(control group),6,12 μg/ml ellagic acid respectively, then the cells were counted at 24,48,72 h after culture. Chemotaxis experiment and Western Blot were conducted to observe the effects of ellagic acid on chemotaxic movement of MDA-MB-231 cells and SDF-1α signaling pathway activation. The data were analyzed using repeated measurement analysis of variance, and pairwise comparison was performed using the SNK-q analysis.

Results

Compared with the control group, cell counts in 6,12 μg/ml ellagic acid treatment groups were significantly reduced at 24, 48, 72 h. Repeated measurement analysis of variance indicated that the comparison between groups(F=4875.56, P=0.00) and among the three time points(F=670.727, P=0.00)showed a statistically significant difference and the interaction existed between group and time(F=122.92, P=0.00). It showed that ellagic acid can significantly inhibit the proliferation of breast cancer cells MDA-MB-231. Chemotaxis experiment of breast cancer cells showed that chemotaxic cells were (14.00±1.00)×10⁵/ml,(7.70±0.58)×10⁵/ml, (3.00±1.00)×10⁵/ml in each group respectively, and the difference was statistically significant (F=117.57,P=0.00 ). Western Blot result showed that ellagic acid significantly inhibited CXCR4 expression and activation of AKT signaling pathway by SDF1α/CXCR4 in breast cancer cells.

Conclusion

Ellagic acid can inhibit the proliferation and SDF1α/CXCR4 mediated chemotaxic movement of breast cancer cells MDA-MB-231 and regress the activation of SDF1α/CXCR4 signaling pathway, which may have potential value in the prevention of breast cancer recurrence and metastasis.

Key words: Ellagic acid, Breast neoplasms, Receptors, CXCR4

表1 不同浓度鞣花酸组在不同时间点的细胞计数比较(×10⁵/ml,±s)

组别	重复次数	24 h	48 h^c	72 h^d
0 μg/ml	3	4.90±0.31	11.20±0.57	20.50±0.75
6 μg/ml^a	3	3.70±0.57	7.80±0.49	12.80±0.42
12 μg/ml^b	3	2.80±0.42	3.90±0.61	5.20±0.51

表1 不同浓度鞣花酸组在不同时间点的细胞计数比较(×10⁵/ml,±s)

组别	重复次数	24 h	48 h^c	72 h^d
0 μg/ml	3	4.90±0.31	11.20±0.57	20.50±0.75
6 μg/ml^a	3	3.70±0.57	7.80±0.49	12.80±0.42
12 μg/ml^b	3	2.80±0.42	3.90±0.61	5.20±0.51

表2 鞣花酸处理后各组MDA-MB-231 的趋化细胞数

组别	重复次数	趋化细胞数(×10⁵/ml, $\bar{x}$ ±s)	统计量	P值
0 μg/ml	3	14.00±1.00
6 μg/ml	3	7.70±0.58^a	117.57	0.000
12 μg/ml	3	3.00±1.00^b

表2 鞣花酸处理后各组MDA-MB-231 的趋化细胞数

组别	重复次数	趋化细胞数(×10⁵/ml, $\bar{x}$ ±s)	统计量	P值
0 μg/ml	3	14.00±1.00
6 μg/ml	3	7.70±0.58^a	117.57	0.000
12 μg/ml	3	3.00±1.00^b

图1 趋化因子受体4(CXCR4)的Western Blot 分析

图2 蛋白激酶B(AKT)及磷酸化AKT(P-AKT)的Western Blot 分析

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Effect of ellagic acid on proliferation and SDF1α/CXCR4 signal path in breast cancer cells MDA-MB-231

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Effect of ellagic acid on proliferation and SDF1α/CXCR4 signal path in breast cancer cells MDA-MB-231