Department of Medical Oncology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China.
Int J Mol Med. 2011 Dec;28(6):985-91. doi: 10.3892/ijmm.2011.790. Epub 2011 Sep 1.
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 antitumoral 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 anti-tumor 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 µg/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 p27Kip1. 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.
曲妥珠单抗能提高细胞毒药物（如紫杉醇和蒽环类药物）对 HER2 过表达乳腺癌细胞的疗效。丁酸钠（NaB），一种组蛋白去乙酰化酶抑制剂，具有抗肿瘤特性。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仍存在争议。为了阐明 NaB 与曲妥珠单抗联合治疗是否对 HER2 过表达乳腺癌细胞系 SKBR3 具有抗肿瘤作用，用 NaB 单独或与曲妥珠单抗联合处理 SKBR3 细胞，并分析对增殖和细胞周期进程的影响。与 NaB 或曲妥珠单抗单独处理相比，NaB（4mmol/L）和曲妥珠单抗（20μg/ml）联合处理显著增加了对 SKBR3 乳腺癌细胞的生长抑制作用。NaB 和曲妥珠单抗联合的生长抑制作用伴随着周期蛋白依赖性激酶抑制剂 p27Kip1 的 mRNA 和蛋白水平升高。相比之下，这种作用在 HER2 阴性 HCC1937 细胞中不存在。总之，曲妥珠单抗显著提高了 NaB 对体外 HER2 过表达乳腺癌细胞系的抗肿瘤作用。
