Enhancement of Radiation Effects by Ursolic Acid in BGC-823 Human Adenocarcinoma Gastric Cancer Cell Line

PLoS One. 2015 Jul 15;10(7):e0133169. doi: 10.1371/journal.pone.0133169. eCollection 2015.

Abstract

Recent research has suggested that certain plant-derived polyphenols, i.e., ursolic acid (UA), which are reported to have antitumor activities, might be used to sensitize tumor cells to radiation therapy by inhibiting pathways leading to radiation therapy resistance. This experiment was designed to investigate the effects and possible mechanism of radiosensitization by UA in BGC-823 cell line from human adenocarcinoma gastric cancer in vitro. UA caused cytotoxicity in a dose-dependent manner, and we used a sub-cytotoxicity concentration of UA to test radioenhancement efficacy with UA in gastric cancer. Radiosensitivity was determined by clonogenic survival assay. Surviving fraction of the combined group with irradiation and sub-cytotoxicity UA significantly decreased compared with the irradiation group. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), down-regulated Ki-67 level and improved apoptosis. In conclusion, as UA demonstrated potent antiproliferation effect and synergistic effect, it could be used as a potential drug sensitizer for the application of radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line, Tumor
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Radiation, Ionizing
  • Radiation-Sensitizing Agents / pharmacology
  • Radiation-Sensitizing Agents / therapeutic use*
  • Reactive Oxygen Species / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / radiotherapy
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*
  • Ursolic Acid

Substances

  • Ki-67 Antigen
  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species
  • Triterpenes

Grants and funding

Supported by grants from the National Natural Science Foundation of China (Grant No. 81172094), Top Six Talents Project of Jiangsu Province (Grant No. 2011ws005), and Medical Science and Technology Development Projects of Nanjing (Grant No. ZKX10011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.