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[Effects and its mechanism of Nimotuzumab on radiosensitivity of esophageal carcinoma ECA-109 and TE-13 cell lines].
- Source :
-
Zhonghua zhong liu za zhi [Chinese journal of oncology] [Zhonghua Zhong Liu Za Zhi] 2016 Oct 23; Vol. 38 (10), pp. 732-738. - Publication Year :
- 2016
-
Abstract
- Objective: To investigate the effects of nimotuzumab on radiosensitivity of ECA-109 and TE-13 esophageal carcinoma cell lines and explore its possible mechanism. Methods: The ECA-109 and TE-13 cells were divided into control group, irradiation group, medicine group, and combined group (irradiation + medicine). In the combined group, ECA-109 and TE-13 cells were treated with nimotuzumab for 24 h before irradiation, and the cells were collected 2 h after irradiation. The radiosensitizing effects of nimotuzumab on ECA-109 and TE-13 cells were evaluated by clone formation assay. Cell apoptosis was detected by flow cytometry. Western blotting was used to evaluate the expression of EGFR, p-EGFR, DNA-PKcs, p-DNA-PKcs and γH2AX. Results: The values of D <subscript>q</subscript> (quasithreshold dose), D <subscript>0</subscript> (mean lethal dose)and SF <subscript>2</subscript> (surviving fraction at 2 Gy) of ECA-109 and TE-13 cells in the combined group were significantly lower than those of the radiation group (for ECA-109 cells, 1.11 vs. 1.72, 1.40 vs. 2.14, 0.42 vs. 0.66, respectively; for TE-13 cells, 0.41 vs. 0.46, 0.43 vs. 0.65, 0.40 vs. 0.71, respectively (all P <0.05). The sensitivity enhancement ratio (SER) of ECA-109 and TE-13 cells were 1.35 and 1.43, respectively. Flow cytometry showed that the apoptosis rate of ECA-109 and TE-13 cells in the combined group were significantly higher than those of the radiation group [for ECA-109 cells, (41.31±1.52)% vs. (9.54±0.52)%; for TE-13 cells, (46.28±0.28)% vs. (11.32±0.31)%, both P <0.01]. Western blotting showed that the expression levels of EGFR and DNA-PKcs were not significantly different in all groups (all P >0.05). Compared with those of the control group, p-EGFR and p-DNA-PKcs of the radiation group were significantly higher in both cell lines ( P <0.05), and the γH2AX levels in the radiation group and medicine group were significantly higher than that of the control group ( P <0.05). Compared with those of the radiation group and medicine group, p-EGFR and p-DNA-PKcs protein expression in the combined group were decreased significantly ( P <0.05), while γH2AX protein expression was significantly increased ( P <0.05). Conclusions: Nimotuzumab can enhance the radiosensitivity of esophageal cancer ECA-109 and TE-13 cells. The potential mechanism may be related to the inhibition of EGFR phosphorylation and down-regulation of DNA damage repair proteins. The radiosensitizing effect of nimotuzumab is greater on poorly differentiated esophageal cancer cells.
- Subjects :
- Apoptosis
Cell Line, Tumor
Chemoradiotherapy
DNA-Activated Protein Kinase metabolism
Down-Regulation
ErbB Receptors metabolism
Esophageal Neoplasms drug therapy
Esophageal Neoplasms metabolism
Esophageal Neoplasms pathology
Histones metabolism
Humans
Lethal Dose 50
Neoplasm Proteins metabolism
Nuclear Proteins metabolism
Antibodies, Monoclonal, Humanized pharmacology
Esophageal Neoplasms radiotherapy
Radiation Tolerance drug effects
Radiation-Sensitizing Agents pharmacology
Subjects
Details
- Language :
- Chinese
- ISSN :
- 0253-3766
- Volume :
- 38
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Zhonghua zhong liu za zhi [Chinese journal of oncology]
- Publication Type :
- Academic Journal
- Accession number :
- 27784455
- Full Text :
- https://doi.org/10.3760/cma.j.issn.0253-3766.2016.10.004