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Anticancer Res. 2004 May-Jun;24(3a):1519-24.

Id3-mediated enhancement of cisplatin-induced apoptosis in a sarcoma cell line MG-63.

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Department of Immunology, Tokyo Medical University, Shinjuku-ku, Tokyo, 160-8402, Japan.


The molecular mechanism(s) underlying the resistance to cis-diamminedichloroplatinum (CDDP)-induced growth inhibition include DNA repair, apoptosis and cell cycle progression. Inhibitor of differentiation (Id) proteins, which belong to the group of helix-loop-helix proteins, regulate cell cycle progression, differentiation and apoptosis. We examined whether CDDP exposure modulates the expression pattern of Ids and whether ectopic expression of Ids influences CDDP-induced cell death. Cell growth was assessed by WST-8 assay kit. Reactive oxygen species (ROS) was evaluated by flow cytometry using dihydroethidium. MG-63 sarcoma cells were stimulated with CDDP for various times and Id expression was assessed by reverse transcription-polymerase chain reaction. CDDP induced a considerable transient up-regulation of Id3 mRNA, but not Id2, 1-2 h after stimulation. Enforced expression of Id3 caused the MG-63 sarcoma cells to be more sensitive to CDDP-induced growth inhibition, through generation of ROS and caspase-3 activation. Together, our results suggest that CDDP-induced cell death appears to involve Id3.

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