Increased expression of metallothionein is associated with irinotecan resistance in gastric cancer.
To gain insight into clinically relevant mechanisms of irinotecan resistance, we undertook oligonucleotide microarray analyses on paired malignant effusion samples obtained from eight gastric cancer patients treated with weekly irinotecan. Pretreatment and posttreatment (48 h) effusion samples were obtained for each patient, and the change in expression profile was compared between clinical responders and nonresponders. When differences in the expression of genes were examined using SAM (Significance Analysis of Microarrays) software, five isoforms of the metallothionein family were identified to have significantly higher signal log ratios in five nonresponders, compared with three responders. Compared with control cells, metallothionein 1X (MT1X)-transfected AGS cells showed a 1.4-fold higher irinotecan IC(50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and tended to form more colonies. These findings collectively suggest that irinotecan-induced up-regulation of metallothionein might be associated with irinotecan resistance in patients with gastric cancer, although it remains to be confirmed in a larger data set.
Chun
Jong Ho
JH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
Kim
Hark Kyun
HK
Kim
Eugene
E
Kim
In-Hoo
IH
Kim
Ju Han
JH
Chang
Hee Jin
HJ
Choi
Il Ju
IJ
Lim
Hyeong-Seok
HS
Kim
Il-Jin
IJ
Kang
Hio Chung
HC
Park
Jae-Hyun
JH
Bae
Jae-Moon
JM
Park
Jae-Gahb
JG
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; C581554:metallothionein1X, human; D000077146:Irinotecan; D008668:Metallothionein; D002166:Camptothecin