Abstract
A major problem which is poorly understood in the management of bladder cancer is low sensitivity to chemotherapy and high recurrence after transurethral resection. Insulin-like growth factor 1 receptor (IGF-1R) signaling plays a very important role in progression, invasion and metastasis of bladder cancer cells. In this study, we investigated whether IGF-1R was involved in the growth stimulating activity and drug resistance of bladder cancer cells. The results showed: The mRNAs of IGF-1, IGF-2 and IGF-1R 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; T24 cell responded far better to growth stimulation by IGF-1 than did normal urothelial cells; blockage of IGF1R by antisense oligodeoxynucleotide (ODN) significantly inhibited the growth of T24 cell and enhanced sensitivity and apoptosis of T24 cells to mitomycin (MMC). These results suggested that blockage of IGF-IR signaling might potentially contribute to the treatment of bladder cancer cells which are insensitive to chemotherapy.
MeSH terms
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Antibiotics, Antineoplastic / agonists*
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Apoptosis / drug effects
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Apoptosis / genetics
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Autocrine Communication / drug effects
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Autocrine Communication / genetics
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Carcinoma, Transitional Cell / drug therapy
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Carcinoma, Transitional Cell / metabolism*
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Carcinoma, Transitional Cell / physiopathology
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Cell Division / drug effects
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Cell Division / genetics
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Cytotoxins / agonists*
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Drug Resistance, Neoplasm / physiology*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Gene Targeting
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Humans
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / pharmacology
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Insulin-Like Growth Factor II / genetics
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Microscopy, Electron
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Mitomycin / agonists*
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Oligodeoxyribonucleotides, Antisense / pharmacology
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Protein Synthesis Inhibitors / pharmacology
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RNA, Messenger / metabolism
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Receptor, IGF Type 1 / antagonists & inhibitors
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Receptor, IGF Type 1 / biosynthesis*
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Receptor, IGF Type 1 / genetics
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Tumor Cells, Cultured / ultrastructure
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Urinary Bladder Neoplasms / drug therapy
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Urinary Bladder Neoplasms / metabolism*
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Urinary Bladder Neoplasms / physiopathology
Substances
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Antibiotics, Antineoplastic
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Cytotoxins
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Oligodeoxyribonucleotides, Antisense
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Protein Synthesis Inhibitors
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RNA, Messenger
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Mitomycin
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Insulin-Like Growth Factor I
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Insulin-Like Growth Factor II
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Receptor, IGF Type 1