Inhibition of ICAM2 induces radiosensitization in oral squamous cell carcinoma cells

T Ishigami1, K Uzawa, K Fushimi

  • 1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Insights

Intercellular adhesion molecule 2 (ICAM2) promotes oral squamous cell carcinoma (OSCC) radioresistance. Silencing ICAM2 with small interfering RNA (siRNA) enhances radiosensitivity and antitumor effects in OSCC, suggesting ICAM2 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Oral squamous cell carcinoma (OSCC) exhibits radioresistance, a major challenge in radiotherapy.
  • Previous studies identified potential genes linked to OSCC radioresistance using gene expression profiling.

Purpose of the Study:

  • To investigate the role of intercellular adhesion molecule 2 (ICAM2) in OSCC radioresistance.
  • To evaluate the efficacy of combining ICAM2 small interfering RNA (siRNA) with X-ray irradiation for OSCC treatment.

Main Methods:

  • Utilized Affymetrix GeneChip for gene identification.
  • Employed small interfering RNA (siRNA) to downregulate ICAM2 expression in OSCC cells.
  • Assessed radiosensitivity, apoptosis (caspase-3 activation, AKT phosphorylation), and radioresistance phenotypes.
  • Investigated the effects of ICAM2 overexpression on radiosensitivity.

Main Results:

  • Downregulation of ICAM2 via siRNA significantly enhanced OSCC cell radiosensitivity.
  • ICAM2 silencing led to increased apoptosis, evidenced by caspase-3 activation and AKT phosphorylation (ser473).
  • Overexpression of ICAM2 conferred greater resistance to X-ray irradiation, demonstrating a radioresistance phenotype.

Conclusions:

  • ICAM2 plays a crucial role in mediating radioresistance in oral squamous cell carcinoma.
  • ICAM2 silencing enhances sensitivity to radiotherapy, indicating its potential as a therapeutic target.
  • Combination therapy of ICAM2 siRNA and X-ray irradiation shows promise for improving OSCC treatment outcomes.