Heavy ion beams induce survivin expression in human hepatoma SMMC-7721 cells more effectively than X-rays

Acta Biochim Biophys Sin (Shanghai). 2007 Aug;39(8):575-82. doi: 10.1111/j.1745-7270.2007.00314.x.

Abstract

High linear energy transfer (LET) heavy ion radiation is more effective in inducing biological damage than low-LET X-rays or gamma-rays. Heavy ion beam provides good dose localization (Bragg peak) in critical cancer tissue and gives higher relative biological effectiveness in cell killing across the dose peak, so high-LET heavy ion beam is superior to low-LET radiation in cancer treatment. Survivin, as a member of the inhibitor of apoptosis protein family, might help cancerous cells to overcome the G2/M apoptotic checkpoint and favor the aberrant progression of transformed cells through mitosis. Survivin expression in the human hepatoma SMMC-7721 cell line after exposure to low-LET X-ray and high-LET carbon ion irradiation was investigated in this study. Compared with X-ray irradiation, the carbon ion beam clearly caused G2/M arrest and promoted the expression of the survivin gene in a dose-dependent manner. Clonogenic survival assay showed that SMMC-7721 cells were more radiosensitive to the high-LET carbon ions than to the X-rays, and the radiosensitivity was promoted after treatment with specific survivin short interfering RNA. Differential survivin expression at both transcriptional and translational levels was found for SMMC-7721 cells following low- and high-LET irradiation. The overexpression of survivin in SMMC-7721 cells is probably an important reason why the cancerous cells have radioresistance to strong stimulus such as dense ionizing high-LET radiation. However, the direct killing effect on cancerous cells by high-LET radiation might be more significant than the apoptosis inhibition through the overexpression of survivin following heavy ion irradiation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Carbon
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / radiotherapy*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Radiation
  • G2 Phase / radiation effects
  • Heavy Ions*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Linear Energy Transfer
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / radiotherapy*
  • Mitosis / radiation effects
  • Radiation Tolerance
  • Time Factors
  • X-Rays

Substances

  • Inhibitor of Apoptosis Proteins
  • Carbon