Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Breast Cancer Res Treat. 2011 Jan;125(1):55-63. doi: 10.1007/s10549-010-0825-z. Epub 2010 Mar 12.
Here we evaluated the cytotoxic effects of a combination of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and taxanes in human breast cancer cell lines. Combination treatment with taxane and SAHA had a synergistic cytotoxic effect against taxane-resistant breast cancer cells. Oligonucleotide microarray analysis identified 28 genes (MAPK13, ATP2C1, ANKRD57, MT1G, RGL4, C12orf49, EXOC6, RAB4A, TM9SF3, IFNGR1, DMD, HCG9, KIFC3, SYNGR3, NDRG4, NT5E, EOMES, SMC4, LANCL1, SCHIP1, and 8 ESTs) whose expression correlated with the combined effect of paclitaxel and SAHA. Twelve of these genes were down-regulated in cell lines that were paclitaxel-resistant but combination synergistic. SAHA induced NT5E mRNA expression in paclitaxel-resistant YCC-B1 cell. Our results indicate that a combination of taxane and SAHA could be efficacious for the treatment of breast cancer and that genes involved in the synergistic response to paclitaxel and SAHA could serve as biomarkers to predict therapeutic response in breast cancer patients.
在这里，我们评估了组蛋白去乙酰化酶抑制剂 SAHA 和紫杉烷类药物联合应用对人乳腺癌细胞系的细胞毒性作用。紫杉烷类药物和 SAHA 的联合治疗对紫杉烷类耐药的乳腺癌细胞具有协同的细胞毒性作用。寡核苷酸微阵列分析鉴定出 28 个基因（MAPK13、ATP2C1、ANKRD57、MT1G、RGL4、C12orf49、EXOC6、RAB4A、TM9SF3、IFNGR1、DMD、HCG9、KIFC3、SYNGR3、NDRG4、NT5E、EOMES、SMC4、LANCL1、SCHIP1 和 8 个 ESTs），其表达与紫杉醇和 SAHA 的联合作用相关。这些基因中有 12 个在紫杉醇耐药但联合协同的细胞系中下调。SAHA 诱导紫杉醇耐药的 YCC-B1 细胞中 NT5E mRNA 的表达。我们的结果表明，紫杉烷类药物和 SAHA 的联合应用可能对乳腺癌的治疗有效，而参与紫杉醇和 SAHA 协同反应的基因可以作为预测乳腺癌患者治疗反应的生物标志物。
