Comprehensive evaluation of the response of genes to the administration of the antitumor drug S-1 using a low density array

Int J Oncol. 2015 Feb;46(2):569-77. doi: 10.3892/ijo.2014.2754. Epub 2014 Nov 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Drug Combinations
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Microarray Analysis
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Oxonic Acid / administration & dosage*
  • Tegafur / administration & dosage*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Neoplasm Proteins
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid