Department of Breast Surgery, Maternity and Child Health Care of Zaozhuang, Zaozhuang, Shandong, China (mainland).
Med Sci Monit. 2019 Nov 28;25:9058-9066. doi: 10.12659/MSM.914486.
BACKGROUND Breast cancer is a common malignant tumor worldwide. Despite the huge advances in modern medicine, many patients still face a high risk of recrudescent and metastatic breast cancer. Berberine was widely implemented in clinic treatment of breast cancer. This study was performed to contribute to a better understanding on the mechanisms underlying berberine affecting breast cancer. MATERIAL AND METHODS We mined survival data of metadherin (MTDH) in breast cancer patients through Kaplan-Meier Plotter and analyzed the transcriptional and posttranscriptional expression profile of MTDH in several breast cancer cell lines. The cell viability and MTDH mRNA level were detected under the si-MTDH vector and different concentrations of berberine. The MTDH-expression vector was transfected into MCF-7 and MDA-MB-231 cells, and the changes of cell viability and apoptosis were determined after berberine (50 μM) treatment. RESULTS High MTDH expression was related to worse relapse-free survival (RFS) of breast cancer (P-value=6.2e-08). High-expressed MTDH is common in breast cancer cells, compared with that in normal breast cells (P<0.01). MTDH knockout could inhibit the viabilities of MCF-7 and MDA-MA-231 cells (P<0.01). When the concentration was higher than 10 μM, the suppressive effects of berberine on viability and MTDH reached significant level. As MTDH expression increased, the enhanced apoptosis rates of breast cancer cells by berberine were remarkably inhibited. CONCLUSIONS High-expressed MTDH was helpful to cell proliferation and survival in breast cancer. The anti-cancer ability of berberine in breast cancer may be partially dependent on the regulation of MTDH.
乳腺癌是一种常见的恶性肿瘤,在全世界范围内都有发生。尽管现代医学取得了巨大进步,但许多患者仍面临着乳腺癌复发和转移的高风险。小檗碱在乳腺癌的临床治疗中得到了广泛的应用。本研究旨在更好地了解小檗碱影响乳腺癌的机制。
我们通过 Kaplan-Meier Plotter 挖掘了乳腺癌患者中 metadherin(MTDH)的生存数据,并分析了几种乳腺癌细胞系中 MTDH 的转录和转录后表达谱。在 si-MTDH 载体和不同浓度小檗碱的作用下,检测细胞活力和 MTDH mRNA 水平。将 MTDH 表达载体转染到 MCF-7 和 MDA-MB-231 细胞中,然后用 50μM 小檗碱处理后,检测细胞活力和凋亡的变化。
高 MTDH 表达与乳腺癌的无复发生存(RFS)较差相关(P 值=6.2e-08)。与正常乳腺细胞相比,高表达的 MTDH 在乳腺癌细胞中更为常见(P<0.01)。MTDH 敲除可抑制 MCF-7 和 MDA-MA-231 细胞的活力(P<0.01)。当浓度高于 10μM 时,小檗碱对活力和 MTDH 的抑制作用达到显著水平。随着 MTDH 表达的增加,小檗碱增强乳腺癌细胞凋亡的作用显著受到抑制。
高表达的 MTDH 有助于乳腺癌细胞的增殖和存活。小檗碱在乳腺癌中的抗癌能力可能部分依赖于 MTDH 的调节。