Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line
Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line
复制标题
曲妥珠单抗增强组蛋白脱乙酰酶抑制剂丁酸钠对 HER2 过表达乳腺癌细胞系的抗肿瘤作用
DOI：
10.3892/ijmm.2011.790
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发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Guan, Xiaoxiang
中科院分区：
文献类型：
--
作者：
Chen, Weiwei;Wei, Feng;Guan, Xiaoxiang
曲妥珠单抗具有改善细胞毒性药物（如紫杉醇和蒽环类药物）对HER 2过表达乳腺癌细胞的作用的功效。丁酸钠（NaB）是一种组蛋白去乙酰化酶抑制剂，具有抗肿瘤作用。然而，曲妥珠单抗是否以及如何具有协同NaB对乳腺癌细胞的抗肿瘤作用的潜力仍然不明确。为了阐明NaB和曲妥珠单抗联合治疗是否对HER 2过表达乳腺癌细胞系发挥抗肿瘤作用，SKBR 3细胞用NaB单独或与曲妥珠单抗联合治疗，并分析对增殖和细胞周期进展的影响。与NaB或曲妥珠单抗单独治疗相比，NaB（4 mmol/l）和曲妥珠单抗（20 μ g/ml）联合治疗显著增加了对SKBR 3乳腺癌细胞的生长抑制作用。NaB和曲妥珠单抗组合的生长抑制作用伴随着细胞周期蛋白依赖性激酶抑制剂p27（Kipl）的mRNA和蛋白水平升高。相反，这种作用在HER 2阴性HCC 1937细胞中不存在。总之，曲妥珠单抗显著提高了NaB对HER 2过表达乳腺癌细胞系的体外抗肿瘤作用。
Trastuzumab has efficacy to improve the effect of cytotoxic drugs, such as paclitaxel and anthracyclin, against HER2-overexpressing breast cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, is known to have anti-tumoral properties. However, whether and how trastuzumab possesses the potential to synergize the anti-tumor effect of NaB on breast cancer cells is still equivocal. To elucidate whether combined treatment with NaB and trastuzumab exerts antitumor effects on a HER2-overexpressing breast cancer cell line, SKBR3 cells were treated with NaB alone or in combination with trastuzumab, and the effects on proliferation and cell cycle progression were analyzed. Combinatory treatment with NaB (4 mmol/l) and trastuzumab (20 mu g/ml) significantly increased the growth-inhibitory effect on SKBR3 breast cancer cells, in comparison to NaB or trastuzumab treatment alone. The growth-inhibitory effect of the combination of NaB and trastuzumab was accompanied by elevated mRNA and protein levels of the cyclin-dependent kinase inhibitor p27(Kipl). In contrast, this effect was absent in HER2-negative HCC1937 cells. In conclusion, trastuzumab significantly improved the antitumor effect of NaB on HER2-overexpressing breast cancer cell line in vitro.