Cellular sensitivity determinants to docetaxel in human gastrointestinal cancers.
beta-tubulin (beta-TUB), Bcl-XL, and additionally glutathione S-transferase pi (GSTpi) were found to participate in sensitivity to docetaxel (TXT) in 7 human gastrointestinal cancer cell lines. The gene expression level of beta-TUB, Bcl-XL, and GSTpi was closely correlated with the IC50 for TXT. beta-TUB amount related to TXT resistance, and GST activity was correlated with IC50 for TXT in the 30-min treatment setting. Bcl-XL transfection increased TXT resistance of COLO201 cells, whereas GST inhibition by ethacrynic acid enhanced TXT cytotoxicity. Continuous TXT treatment increased beta-TUB and GSTpi expression, but the increased GSTpi mRNA was observed in TXT-resistant HCC-48 cells alone.
Park
Ji Seon
JS
Department of Biochemistry and Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Yamamoto
Wataru
W
Sekikawa
Takashi
T
Matsukawa
Masaaki
M
Okamoto
Ryo
R
Sasaki
Masao
M
Ukon
Kei
K
Tanimoto
Keiji
K
Kumazaki
Tsutomu
T
Nishiyama
Masahiko
M
D002455:Cell Division / Q000187:drug effects; D000077143:Docetaxel; D004976:Ethacrynic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53 / Q000235:genetics; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000235:genetics; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D043823:Taxoids; D014404:Tubulin; D051020:bcl-X Protein; D000077143:Docetaxel; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D004976:Ethacrynic Acid; D017239:Paclitaxel