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Updated: Aug 7, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Id3-mediated enhancement of cisplatin-induced apoptosis in a sarcoma cell line MG-63
Takashi Koyama1, Hidekazu Suzuki, Atsuhiro Imakiire
1Department of Immunology, Tokyo Medical University, Shinjuku-ku, Tokyo, 160-8402, Japan.
Abstract:
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.
Insights
cis-diamminedichloroplatinum (CDDP) resistance involves DNA repair, apoptosis, and cell cycle. Inhibitor of differentiation 3 (Id3) expression increases after CDDP exposure, enhancing CDDP-induced cell death via reactive oxygen species and caspase-3 activation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Resistance to cis-diamminedichloroplatinum (CDDP) is a significant challenge in cancer therapy.
- Inhibitor of differentiation (Id) proteins regulate key cellular processes including cell cycle progression, differentiation, and apoptosis.
- Understanding the role of Id proteins in CDDP resistance is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the effect of CDDP exposure on the expression of Id proteins in MG-63 sarcoma cells.
- To determine whether ectopic expression of Id proteins influences CDDP-induced cell death.
- To elucidate the molecular mechanisms underlying CDDP resistance and sensitivity.
Main Methods:
- MG-63 sarcoma cells were treated with CDDP.
- Cell growth was assessed using a WST-8 assay kit.
- Reactive oxygen species (ROS) generation was evaluated by flow cytometry.
- Id protein expression was analyzed using reverse transcription-polymerase chain reaction (RT-PCR).
- Caspase-3 activation was measured to assess apoptosis.
Main Results:
- CDDP treatment led to a transient upregulation of Id3 mRNA, but not Id2, within 1-2 hours.
- Enforced expression of Id3 sensitized MG-63 cells to CDDP-induced growth inhibition.
- Id3 overexpression promoted CDDP-induced cell death through increased ROS generation and caspase-3 activation.
Conclusions:
- CDDP-induced cell death in MG-63 sarcoma cells appears to involve the Id3 protein.
- Id3 may play a significant role in modulating cellular response to CDDP treatment.
- Targeting Id3 could be a potential therapeutic strategy to overcome CDDP resistance in certain cancers.
