We have previously demonstrated that ectopic insulin-like growth factor binding protein 3 (IGBBP3) expression enhanced lymph node metastasis of OSCC cells. However, the survival analysis of OSCC patients with high levels of IGFBP3 had an increased survival rate compared to those with low levels of IGFBP3. Furthermore, we found that ectopic IGFBP3 expression enhanced the radiation-induced cell-killing effect, indicating that the sensitive effects of IGFBP3 on radiation treatment might contribute to the better survival of OSCC after conventional treatment. In vivo, we discovered that ectopic IGFBP3 expression after 8-Gy radiation treatments can reduce tumor weight, volume and metastasis ability, but did not decrease tumor lymphangiogenesis. In vitro, ectopic IGFBP3 expression did not affect radiation-induced cell cycle arrest, but enhance radiation-induced cell death as evidenced by doubling staining with PI and annexin V. Additionally, we found that ectopic IGFBP3 expression increased the reactive oxygen species production and decreased mitochondrial membrane potential by flow cytometry. We will further investigate the roles of IGFBP3 in mitochondria upon radiation treatment.
