Global gene expression changes including drug metabolism and disposition induced by three-dimensional culture of HepG2 cells-Involvement of microtubules.
Constitutive upregulation and a higher degree of induction of drug metabolism and disposition-related genes were found in a three-dimensional HepG2 culture. The upregulated genes are believed to be regulated by different regulatory factors. Global gene expression analysis using the Affymetrix GeneChip indicated that altered expression of microtubule-related genes may change the expressed levels of drug metabolizing and disposition genes. Stabilization of microtubule molecules with docetaxel, a tubulin-stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those found in the three-dimensional culture, indicating that the culture environment affects drug metabolism functions in HepG2 cells.
Horiuchi
Shin-Ichiro
S
Division of Pharmacology, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan.
Ishida
Seiichi
S
Hongo
Tomokatsu
T
Ishikawa
Youichi
Y
Miyajima
Atsuko
A
Sawada
Jun-Ichi
J
Ohno
Yasuo
Y
Nakazawa
Ken
K
Ozawa
Shogo
S
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D018929:Cell Culture Techniques; D000090702:Constitutive Androstane Receptor; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D000077143:Docetaxel; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011987:Receptors, Steroid / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation
D001189:Aryl Hydrocarbon Hydroxylases; D000090702:Constitutive Androstane Receptor; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D000077143:Docetaxel; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010089:Oxidoreductases, N-Demethylating; D004364:Pharmaceutical Preparations; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D043823:Taxoids; D014157:Transcription Factors; C585599:CYP2B6 protein, human; C510163:CYP3A4 protein, human; C421109:multidrug resistance-associated protein 1