title: [Molecular mechanism of radiosensitizing effect of paclitaxel].
abstract: OBJECTIVE
  Paclitaxel is a radiosensitizer which may stabilize microtubules, block the G2/M phase of the cell cycle and thus modulate the radioresponsiveness of tumor cells. However, its potential molecular mechanisms of radiosensitization have not been well understood yet. This study was to investigate the radiosensitizing effect of paclitaxel on human oral epithelium carcinoma (KB) cell line and to explore the molecular mechanism of radiosensitization.
  
  
  METHODS
  The survival of KB cells following the treatment with paclitaxel and/or radiation was determined by colony-forming assay. The radiosensitizing effect was evaluated by calculating the sensitizing enhancement ratio (SER) with multi-target single hit model. The cell cycle distribution was analyzed by flow cytometry. Differentially expressed genes related to paclitaxel radiosensitization were screened using human Oligo microarray. Expressions of protein regulating cytokinesis 1 (PRC1) and cyclin B2 genes were confirmed by real-time quantitative PCR.
  
  
  RESULTS
  The proliferation of KB cells was significantly inhibited by paclitaxel combined with ionizing radiation. The SERD0 and SERDq were (2.40 +/- 1.87) and (12.23 +/- 2.81) respectively, when the concentration of paclitaxel was 20 nmol/l. After the treatment with paclitaxel in combination with irradiation, the percentage of G1 phase cells decreased from (48.32 +/- 2.40)% to (15.73 +/- 7.00)% (P<0.01), and the percentage of G2/M phase cells increased from (13.66 +/- 2.16)% to (52.51 +/- 5.02)% (P<0.01). In total 176 differentially expressed genes were identified to be related to paclitaxel radiosensitization. Ten genes were found to regulate cell division, two of which were up-regulated and eight were down-regulated after the treatment. Moreover, the expression of PRC1 and cyclin B2 was decreased.
  
  
  CONCLUSIONS
  The radiosensitizing effect of paclitaxel on KB cells may be due to the down-regulated expression of PRC1 and cyclin B2, resulting in inhibition of mitotic spindle formation and cell necrosis.
authors: Department of Basic Nuclear Medicine, School of Radiation Medicine and Public Health, Medical College of Soochow University, Suzhou, Jiangsu, 215123, P.R. China.
authors: Wan-Wen
authors: WW
authors: Weng
authors: Yu-Jie
authors: YJ
authors: Xu
authors: Jian-Mei
authors: JM
authors: Wan
authors: Zong-Zhan
authors: ZZ
authors: Wang
authors: Wen-Xiu
authors: WX
authors: Ding
authors: Min
authors: M
authors: Liu
authors: Cheng-Jiao
authors: CJ
authors: Hong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056765:Cyclin B2 / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007624:KB Cells; D017239:Paclitaxel / Q000494:pharmacology*; D010315:Particle Accelerators; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D056765:Cyclin B2; C116662:PRC1 protein, human; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel