Enhancement of radiation sensitivity by erlotinib and celecoxib in A549 human lung cancer cell line
10.3760/cma.j.issn.0254-5098.2012.02.020
- VernacularTitle:厄洛替尼和塞来昔布联合应用对人肺腺癌A549细胞放射增敏的研究
- Author:
Jian SUN
;
Ningbo LIU
;
Hongqing ZHUANG
;
Lujun ZHAO
;
Zhiyong YUAN
;
Ping WANG
- Publication Type:Journal Article
- Keywords:
Celecoxib;
Erlotinib;
Lung adenocarcinoma;
Radiosensitization
- From:
Chinese Journal of Radiological Medicine and Protection
2012;32(2):186-190
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of epidermal growth factor receptor and cyclooxygenase-2 pathways in the erlotinib and celecoxib enhanced radiation sensitivity in A549 human lung cancer cell line. Methods IC20 of erlotinib and celecoxibon in A549 human lung cancer cells was measured by MTT assay,Clonogenic assays were used to evaluate the antitumor effects of the drugs and Xirradiation.Flow cytometry was used to assess the apoptosis and cell cycle alteration,and Western blot was used for the detection of Akt and phospho-Akt.Results Both erlotinib and celecoxib could inhibit the proliferation of A549 cells in vitro in a dose-dependent manner and their values of IC20 were (5.15 ± 0.14)and (40.32 ± 1.26) μmol/L,respectively. For radiation survival,the values of Dq,Do,SF2 of the combination of two drugs were lower than those of either drug ( t =6.62,P ＜ 0.05).The SER of celecoxib,erlotinib and their combination were 1.299,1.503 and 2.217,respectively.Flow cytometry assay showed that both celecoxib and erlotinib could enhance radiation-induced G0/G1 arrest,reduce the cell numbmer in S phase,and enhance radiation-induced apoptosis,especially for the combination of drugs.Western blot assay showed that the expressions of Akt protein were similar in all groups.However,pAkt expression was suppresssed by erlotinib and celecoxib,but promoted by radiation.pAkt had the lowest expression in the radiated cells with the treatment of two drugs ( t =4.89,P ＜ 0.05 ).Conclusions The edotinib and/or celecoxib could enhance radiosensitivity probably by increasing cell apoptosis and reducing the number of Sphase cells with low radiosensitivity.
