Docetaxel shows radiosensitization in human hepatocellular carcinoma cells

World J Gastroenterol. 2005 May 21;11(19):2990-3. doi: 10.3748/wjg.v11.i19.2990.

Abstract

Aim: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.

Methods: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time.

Results: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.

Conclusion: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / radiotherapy*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Docetaxel
  • Dose-Response Relationship, Radiation
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / radiotherapy*
  • Oxidation-Reduction
  • Radiation-Sensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Taxoids / pharmacology*

Substances

  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • Taxoids
  • Docetaxel