title: Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array.
abstract: S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takizawa
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fujino
authors.affiliation: Tsukuba Research Center, Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sakamoto
authors.affiliation: Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Uyama
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toba
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kenzaki
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.affiliation: Department of Thoracic, Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tangoku
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010094:Oxonic Acid / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D009363:Neoplasm Proteins; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid