RRC ID 19374
著者 Kim JC, Shin ES, Kim CW, Roh SA, Cho DH, Na YS, Kim TW, Kim MB, Hyun YL, Ro S, Kim SY, Kim YS.
タイトル In vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer.
ジャーナル Anticancer Res
Abstract BACKGROUND:Our primary aim was to evaluate the additive efficacy of histone deacetylase inhibitors (HDACIs) in established treatment regimens for colorectal cancer in concurrence with identifying the clinicopathological markers significantly associated with tumor responsiveness.
PATIENTS AND METHODS:The chemosensitivities of 125 colorectal carcinomas to established regimens [FLOX (5-FU + leucovorin + oxaliplatin) and FLIRI (5-FU + leucovorin + irinotecan)], two biologically targeted drugs (avastin and erbitux), and two hydroxamic acid derivatives (vorinostat, SAHA(R), and a novel candidate, CG2) were comparatively evaluated using an in vitro tumor response assay.
RESULTS:The response rates of tumors (inhibition rate > or =30%) were significantly greater for FLOX and combinations (55.2-68%) compared to FLIRI and combinations (44-63.2%) (p=0.001 to 0.048), except in the case of the CG2 combination. The additive effects of HDACIs on the respective established regimens were considerably greater for non-responsive tumors (64.3-80%) than responsive tumors (32.7-45%) (p< or =0.0001 to 0.008). A number of biological parameters, including less advanced tumors and p53 overexpression, were significantly associated with additive chemosensitivity to HDACIs in combination with FLOX and FLIRI in multivariate analyses (p< or =0.001 to 0.023). Expanding tumor growth, diffuse cytoplasmic carcinoembryonic antigen (CEA) expression and synchronous adenoma were associated with combination regimens with targeted drugs (p=0.013 to 0.032).
CONCLUSION:Our findings show additive chemoresponsiveness of colorectal tumors to HDAC inhibitors in combination with established regimens. The significant parameters associated with combination regimens of targeted drugs and HDACIs may be applied as effective chemosensitive markers in future clinical trials.
巻・号 29(8)
ページ 3027-34
公開日 2009-8-1
PII 29/8/3027
PMID 19661311
MeSH Adenocarcinoma / drug therapy* Adenocarcinoma / enzymology Adenocarcinoma / secondary Adenocarcinoma, Mucinous / drug therapy* Adenocarcinoma, Mucinous / enzymology Adenocarcinoma, Mucinous / secondary Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Cell Proliferation / drug effects Colorectal Neoplasms / drug therapy* Colorectal Neoplasms / enzymology Colorectal Neoplasms / pathology Dose-Response Relationship, Drug Drug Synergism Drug Therapy, Combination Enzyme Inhibitors / therapeutic use* Female Histone Deacetylase Inhibitors* Humans In Vitro Techniques Male Middle Aged Neoplasm Staging Prognosis Prospective Studies Treatment Outcome
IF 1.994
引用数 19
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MKN74(RCB1002)