RRC ID 63794
著者 Han B, Lee-Okada HC, Ishimine M, Orita H, Nishikawa K, Takagaki T, Kajino K, Yokomizo T, Hino O, Kobayashi T.
タイトル Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells.
ジャーナル FEBS Open Bio
Abstract Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a. A combination of CPT-11 and nutlin-3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT-11 in the absence of nutlin-3a. Enhancement of the growth inhibitory activity of CPT-11 by nutlin-3a suggests a possible new combinatorial MM chemotherapy regimen.
巻・号 10(11)
ページ 2375-2387
公開日 2020-11-1
DOI 10.1002/2211-5463.12985
PMID 32961616
PMC PMC7609812
MeSH Antineoplastic Combined Chemotherapy Protocols / pharmacology Antineoplastic Combined Chemotherapy Protocols / therapeutic use* Carboxylesterase / metabolism Cell Death / drug effects Cell Line, Tumor Cell Proliferation / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Imidazoles / pharmacology Imidazoles / therapeutic use Irinotecan / pharmacology Irinotecan / therapeutic use* Mesothelioma / drug therapy* Mesothelioma / genetics Mesothelioma / pathology* Mutagens / toxicity Piperazines / pharmacology Piperazines / therapeutic use Tumor Suppressor Protein p53 / metabolism*
IF 2.231
リソース情報
ヒト・動物細胞 ACC-MESO-1(RCB2292) ACC-MESO-4(RCB2293)