Identification of genes associated with chemosensitivity to SAHA/taxane combination treatment in taxane-resistant breast cancer cells.
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.
Chang
Hyun
H
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Jeung
Hei-Cheul
HC
Jung
Je Jun
JJ
Kim
Tae Soo
TS
Rha
Sun Young
SY
Chung
Hyun Cheol
HC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004357:Drug Synergism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077337:Vorinostat
D000972:Antineoplastic Agents, Phytogenic; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D000077337:Vorinostat; D017239:Paclitaxel