Inositol 1,4,5-trisphosphate (IP3) receptor type1 (IP3R1) modulates the acouisition of cisplatin resistance in bladder cancer cell lines

To investigate the molecules that regulate the acquisition of cis-diamminedichloroplatinum (11) (cisplatin) resistance, we performed cDNA microarrays using two pairs of parental and cisplatin-resistant bladder cancer cell lines. We found a markedly reduced expression of inositol 1,4,5-trisphosphate (IP3) receptor typel (IP(3)R1), endoplasmic reticulum membrane protein, in cisplatin-resistant cells. The suppression Of IP(3)R1 expression using small interfering RNA in parental cells prevented apoptosis and resulted in decreased sensitivity to cisplatin. Contrarily, overexpression Of IP(3)R1 in resistant cells induced apoptosis and increased sensitivity to cisplatin. These results suggest that cisplatin-induced downregulation of IP(3)R1 expression was closely associated with the acquisition of cisplatin resistance in bladder cancer cells. Published online 20 December 2004.