Abstract:

Abstract:Objective
To observe the killing effects of different kinds of radiotherapy methods  and the radiosensitization of cisplatin on lung cancer cells and to explore the role of autophagy  and related mechanisms by in vitro and in vivo experiments.  Methods
Lung cancer cells  A549 were treated with different concentrations (0,1.0，2.5，5.0，10.0，20.0，and 40.0  μmol?L-1) of cisplatin.40 C57BL/6 mice were randomly divided into  control group(n=10),conventional fractionated radiation group(n=10),hyperfractionated radiation  group (n=10),and  combination group (n=10).The tumor-bearing C57BL/6 models were established. MTT assay was used to detect the cell viability;Western blotting method was used to detect the expressions of autoiphagy-relative gene  MAPLC3 and Beclin1  protein of the  mice in various groups;the tumor volumes of the mice were mesured by caliper;the expression levels of MAPLC3Ⅱ,PI3KⅢ,and Beclin1 in tumor tissue were detected by immunohistochemistry.Results With the increasing of cisplatin concentration(>5  μmol?L-1),the cell viability of A549 cells  was decreased significantly; the cell viabilities in  10.0，20.0，and 40.0   μmol?L-1 cisplatin groups were decreased
 compared with control group(0 μmol•L^-1 cisplatin)(P<0.05).Compared with control group,the expression levels of MAPLC3Ⅱ and Beclin1 in A549 cells in the other groups were increased.The tumor volumes were compared,hyperfractionated radiation  group<  combinatin  group< conventional fractionated radiation group<  control group.Compared with control group,the tumor volumes of the mice in the other groups were decreased（P<0.05）.Compared with control group, the expression  levels of MAPLC3Ⅱ,PI3KⅢ, and  Beclin1  in the other groups were increased significantly(P<0.05）,especially in  combination   group.Conclusion The synergistic cytotoxic effect of ciaplatin with irradiation results in a killing effects on lung cancer cells,and autophagy might participate in this process.
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Key words: autophagy；cisplatin； radiotherapy；lung neoplasms, exograft