Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to mitomycin.
OBJECTIVE
To investigate whether insulin-like growth factor I receptor (IGF-IR) was involved in drug resistance of bladder cancer cells.


METHODS
RT-PCR was used to detect the mRNA expression of IGF-I, IGF-II, and IGF-IR in T24 cells and normal urothelial cells. Flow cytometry and MTT tests were used to assess the effect of antisense oligodeoxynucleotide (ODN) on drug sensitivities and apoptosis of T24 cells to mitomycin (MMC). Western blot was used to analyze the effect of ODN on expression of IGF-I R protein.


RESULTS
mRNA of IGF-I, IGF-II, and IGF-IR were strongly expressed in serum-free cultured T24 cell line, whereas normal urothelial cells did not express these factors/receptors or only in trace levels; knockdown of IGF-IR by antisense ODN greatly inhibited the growth of bladder cancer cells and enhanced sensitivity and apoptosis of T24 cells to MMC.


CONCLUSIONS
These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which were insensitive to chemotherapy.
Sun
H Z
HZ
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Wu
S F
SF
Tu
Z H
ZH
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D016685:Mitomycin / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D036341:Intercellular Signaling Peptides and Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; C065700:myotrophin; D016685:Mitomycin; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1