Differential gene expression profile between PC-14 cells treated with free cisplatin and cisplatin-incorporated polymeric micelles.
Cisplatin (CDDP)-incorporated polymeric micelles (CDDP/m) are a macromolecular carrier system possessing a time-modulated decaying property accompanied by sustained release of free drug. The gene expression profiles in nonsmall cell lung cancer PC-14 cells treated with free CDDP and CDDP/m were evaluated by a cDNA expression array for 807 genes. Although the total gene expression profile of the cells treated with CDDP/m approximated that of free CDDP in the hierarchical clustering analysis, a number of genes showed differential expression according to whether the cells had been treated with CDDP or CDDP/m. Ultimately, 50 genes with significant differential expression between cells treated with CDDP and CDDP/m were selected by principal component (PC) analysis and the unpaired t-test. The genes selected, including genes related to cell cycle regulation, apoptosis-related proteins, detoxification, and DNA repair enzymes, were considered to be related to CDDP-induced cytotoxicity. Interestingly, CDDP/m down-regulated the genes encoding integrins and matrix metalloproteinases (MMPs), which play an integral role in tumor invasion, metastasis, and angiogenesis, whereas free CDDP up-regulated them. The results suggest that use of the macromolecular carriers may yield additional therapeutic effects over free drug.
Nishiyama
Nobuhiro
N
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Japan.
Koizumi
Fumiaki
F
Okazaki
Soichiro
S
Matsumura
Yasuhiro
Y
Nishio
Kazuto
K
Kataoka
Kazunori
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis; D003692:Delayed-Action Preparations; D015870:Gene Expression / Q000187:drug effects*; D008024:Ligands; D051379:Mice; D008823:Micelles; D011108:Polymers; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D013347:Subcellular Fractions / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D003692:Delayed-Action Preparations; D008024:Ligands; D008823:Micelles; D011108:Polymers; D012334:RNA, Neoplasm; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D002945:Cisplatin