Altered gene expression by cisplatin in a human squamous cell lung carcinoma cell line.
BACKGROUND
Substantial evidence has disclosed that some cytotoxic agents have complex activities in influencing signal transduction pathways in cells.


METHODS
cDNA microarray analysis was performed after exposing a human squamous cell carcinoma cell line, RERF-LC-AI, to low-dose cisplatin for 5 days. Up-regulated gene expressions were suppressed by small interfering RNA to investigate phenotypic alteration of the cells.


RESULTS
Among 30,000 genes screened, 42 genes showed increases or decreases in expression of more than 2-fold with cisplatin treatment. They included genes with functions involved in apoptosis, cell cycle regulation and DNA metabolism/repair. Suppression of the 5 most significantly altered genes by small interfering RNA resulted in partly reduced apoptosis without altering cytotoxicity of cisplatin.


CONCLUSIONS
Besides direct cytotoxic effects on cells, cisplatin may have indirect effects involving drug resistance, and synergistic effects with other agents.
Yatomi
Mari
M
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takiguchi
Yuichi
Y
Asaka-Amano
Yoshiko
Y
Arai
Makoto
M
Tada
Yuji
Y
Kurosu
Katsushi
K
Sakao
Seiichiro
S
Kasahara
Yasunori
Y
Tanabe
Nobuhiro
N
Tatsumi
Koichiro
K
Seki
Naohiko
N
Kuriyama
Takayuki
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D002945:Cisplatin