Effects and its mechanism of Nimotuzumab on radiosensitivity of esophageal carcinoma ECA-109 and TE-13 cell lines
10.3760/cma.j.issn.0253-3766.2016.10.004
- VernacularTitle:尼妥珠单抗对食管鳞癌ECA-109和TE-13细胞放射敏感性的影响及其发生机制
- Author:
Jun WANG
1
,
2
;
Wen WANG
;
Yin GUO
;
Shaowu JING
;
Kai SHANG
;
Mingchang MIAO
;
Jing WANG
;
Yajing WU
;
Lina LIU
;
Jinming YU
Author Information
1. 300070 天津医科大学肿瘤医院放疗科
2. 050011 石家庄，河北医科大学第四医院放疗科
- Keywords:
Esophageal neoplasms;
Receptor,epidermal growth factor;
Radiation tolerance;
Nimotuzumab
- From:
Chinese Journal of Oncology
2016;38(10):732-738
- CountryChina
- Language:Chinese
-
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 Dq( quasithreshold dose) , D0( mean lethal dose) and SF2(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 theγH2AX 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.
