表柔比星化疗对乳腺癌转移潜能的影响

目的:比较乳腺癌细胞经过表柔比星处理前后的生物学行为,探讨表柔比星化疗对乳腺癌转移潜能的影响及机制。方法:人乳腺癌细胞MCF-7和MDA-MB-231分别给予正常培养和表柔比星6小时处理,通过划痕实验和transwell实验比较两组细胞迁移和侵袭能力的差别。MCF-7细胞经过表柔比星处理不同时间后,通过real-time PCR分析细胞中转移相关蛋白1(Metastasis Associated Protein 1,MTA1)表达水平的变化。建立小鼠4T1乳腺癌模型,观察表柔比星化疗对小鼠肺表面乳腺癌转移灶的数量的影响。结果:划痕实验中,处理组MCF-7和MDA-MB-231细胞24小时内平均划痕愈合距离均显著长于对照组细胞(P0.05);transwell实验中,处理组MDA-MB-231细胞24小时内穿膜细胞数显著多于对照组细胞(P0.01),MCF-7细胞本身侵袭性低难以穿膜;real-time PCR结果显示,表柔比星处理使MCF-7细胞中MTA1转录水平出现显著上调(P0.05);动物实验结果显示,处理组小鼠肺表面转移灶数量显著多于对照组(P0.01)。结论:表柔比星处理可以在体内和体外增强乳腺癌细胞的转移潜能,这一改变可能与其诱导MTA1的表达有关。

Effect of Epirubicin Chemotherapy on Metastatic Potential of Breast Cancer

Objective:To investigate the effect of epirubicin chemotherapy on metastatic potential of breast cancer and its possible mechanisms by comparison of the biological behaviors of epirubicin pre-treatment breast cancer cells with untreated cells.Methods:Human breast cancer MCF-7 and MDA-MB-231 cells were respectively treated with epirubicin for 6 hours or kept in normal culture medium. The migration and invasion capacity of these differently treated cells were assessed by wound-healing assays and transwell assays. Real-time PCR was used to analyze the alteration of mRNA levels of metastasis associated protein 1 (MTA1) in MCF-7 cells treated with epirubicin for different periods of time. Mouse 4T1 breast cancer model was established to observe the effect of epirubicin chemotherapy on the occurrence of surface lung metastases.Results:In the wound-healing assays, cells treated with epirubicin showed greater wound closure between 0 and 24 hours than untreated cells in both cell lines (P < 0.05). In the transwell assays, epirubicin treated MDA-MB-231 cells showed significant increase (P < 0.01) in the numbers of cells invading the Matrigel-coated membrane compared with untreated cells, but the difference in MCF-7 cells was not significant, probably due to their innate low invasive capacity. Real-time PCR showed that epirubicin treatment led to a significant increase (P < 0.05) in the expression of MTA1 mRNA in MCF-7 cells. In tumor-bearing mice, more surface lung metastases were observed in treated mice than untreated ones (P < 0.01).Conclusion:Epirubicin treatment can promote metastasis of breast cancer cells both in vitro and in vivo, and its stimulation of MTA1 is a possible mechanism.