Knockdown of IGF- I R by antisense oligodeoxynucleotide auguments sensitivity of T24 bladder cancer cells to mitomycin

AIM: To investigate whether insulin-like growth factor receptor (IGF-I R) w as involved in drug, resistance of bladder cancer cells. METHODS: RT-PCR wa s used to detect the mRNA expression of IGF-I, IGF-II, and IGF-I R in T24 c ells and normal urothelial cells. Flow cytometry and NM tests were used to assess the effect of antisense oligodeoxynucleotide ( ODN) on drug sensitiv ities and apoptosis of T24 cells to mitomycin (NMC). Western blot was used to analyze the effect of ODN on expression of IGF-I R protein. RESULTS: mRN A of IGF-I, IGF-II, and IGF-I R were strongly expressed in serum-free cultu red T24 cell line, whereas normal urothelial cells did not express these fa ctors/receptors or only in trace levels; knockdown of IGF-I R by antisense ODN greatly inhibited the growth of bladder cancer cells and enhanced sensi tivity and apoptosis of T24 cells to MMC. CONCLUSION: These results suggest ed that blockage of IGF-I R signaling might potentially contribute to the t reatment of bladder cancer cells which were insensitive to chemotherapy.