304 Clinical Department of General Hospital of PLA, Beijing, PR China.
Pharm Biol. 2011 Nov;49(11):1167-72. doi: 10.3109/13880209.2011.575792.
Human epidermal growth factor receptor 2 (HER2) is one of the oncogenes closely associated with the development and prognosis of breast carcinoma. Down-regulation of HER2 mRNA by antisense oligodeoxynucleotide (ASO) HER2 has been suggested to be a feasible treatment for patients with breast carcinoma.
The antitumor effects of ASO HA6722 were investigated in vitro and in vivo.
In this study, SK-BR-3, a HER2-overexpressing breast carcinoma cell line, was used as the model for in vitro experiments. Inhibitory effects of the ASO HA6722 were detected by methyl-thiazoldiphenyl tetrazolium (MTT) assay. Meanwhile, HER2 mRNA levels were monitored by reverse transcription polymerase chain reaction (RT-PCR). The in vivo antitumor effects were evaluated in nude mice xenograft model.
Our results showed that HA6722 alone could inhibit the growth of SK-BR-3 cells in a dose-dependent manner with the IC(50) value of 41.8 ± 8.1 nM. In addition, the antitumor effect of docetaxel (TXT) could be sensitized by low dose of HA6722 both in vitro and in vivo, suggesting that ASO HA6722 could inhibit the growth of breast cancer cells and enhance the cytotoxic effects of TXT.
The combination treatment of TXT and HA6722 could be a more effective approach for breast cancer treatment. The future study should focus on the antitumor effect in other models.
人表皮生长因子受体 2（HER2）是与乳腺癌的发生和预后密切相关的癌基因之一。用反义寡脱氧核苷酸（ASO）HER2 下调 HER2 mRNA 已被认为是治疗乳腺癌患者的一种可行方法。
研究 ASO HA6722 的体内外抗肿瘤作用。
本研究以 HER2 过表达的乳腺癌细胞系 SK-BR-3 为模型进行体外实验。噻唑蓝（MTT）比色法检测 ASO HA6722 的抑制作用。同时，通过逆转录聚合酶链反应（RT-PCR）监测 HER2 mRNA 水平。在裸鼠异种移植模型中评价体内抗肿瘤作用。
我们的结果表明，HA6722 单独作用于 SK-BR-3 细胞，呈浓度依赖性抑制细胞生长，IC50 值为 41.8±8.1 nM。此外，低剂量的 HA6722 可增强紫杉醇（TXT）的体内外抗肿瘤作用，提示 ASO HA6722 可抑制乳腺癌细胞生长，增强 TXT 的细胞毒性作用。
TXT 和 HA6722 的联合治疗可能是治疗乳腺癌的更有效方法。未来的研究应集中在其他模型中的抗肿瘤作用。
