title: [Effect of dihydroartemisinin combined irradiation on the apoptosis of human lung cancer GLC-82 cells and its mechanism study].
abstract: OBJECTIVE
  To study the effect of dihydroartemisinin (DHA) combined irradiation on the apoptosis of human lung cancer GLC-82 cells and to study its mechanism.
  
  
  METHODS
  The growth inhibition rate of GLC-82 cells acted by different concentrations DHA was detected using MTT assay at 24, 48, and 72 h, respectively. Clone forming test was used. With multi-target single-hit model, the radiosensitization effect was assessed by calculating sensitizing enhancement ratio (SER).The effect of DHA combined irradiation on the apoptosis of GLC-82 cell cycle distribution and apoptosis were measured by flow cytometry. The protein expression of p53, p21, Bcl-2, and Bax were detected by Western blot.
  
  
  RESULTS
  Different concentrations DHA (4, 8, 16, 32, 64, and 128 μg/mL) had cytotoxicity on GLC-82 cells. The IC50 for 24, 48, and 72 h was 38.25,20.58, and 10.36 μg/mL, respectively, in obvious dose- and time-dependent manner. The growth inhibition rate was more significantly increased than that of the blank control group (P < 0.01, P<0.05). DHA had sensitization enhancement effect on GLC-82 cells, with SER of 1.4. DHA combined irradiation could obviously change the structure of GLC-82 cells cell cycle and induce apoptosis (with the apoptosis rate of 21.5%), which was significantly different from that of the blank control group (P < 0.05). Western blot showed the expression of p53 and p21 protein could be increased by DHA combined irradiation, and the expression of Bcl-2 protein down-regulated (P <0.01, P <0. 05).
  
  
  CONCLUSIONS
  DHA had stronger cytotoxicity and radiosensitization on GLC-82 cells. Its mechanisms might lie in making the arrest of GLC-82 cells' growth at G0/G1 phase, decreasing the ratio of cells at S phase, restoring the function of p53, decreasing the expression of Bcl-2 protein, and inducing apoptosis in GLC-82 cells.
authors.forename: Zhan-jie
authors.initials: ZJ
authors.lastname: Zuo
authors.forename: Song-tao
authors.initials: ST
authors.lastname: Wang
authors.forename: Li-xiang
authors.initials: LX
authors.lastname: Jiang
authors.forename: Yong-xiang
authors.initials: YX
authors.lastname: Xin
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zi-hao
authors.initials: ZH
authors.lastname: Xu
authors.forename: Jiao-long
authors.initials: JL
authors.lastname: Wang
authors.forename: Jian-dong
authors.initials: JD
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D037621:Artemisinins; D009363:Neoplasm Proteins; D011838:Radiation-Sensitizing Agents; D051028:bcl-2-Associated X Protein; C039060:artenimol