Antisense MDM2 sensitizer of lung cancer cells A549 to ionizing radiations

Lung cancer causes a great number of deaths worldwide, and is a leading cause of cancer death in China. Radiotherapy plays a key role in lung cancer treatments. Currently, however, it is difficult to further improve radiocurability of lung cancers. Murine double minute 2(MDM2), an important gene in tumorigenesis and cell proliferation, might be a suitable target for gene therapy approaches. In this study, the authors designed an antisense drug targeting to MDM2, and detected inhibitory effect of the antisense in A549 cells by RT-PCR and Western Blotting. Subsequently, the radiation-mediated cell killing was detected by Flow Cytometry and proliferative activity was observed by MTT assay. The antisense strategy was employed, too, to achieve partial reduction of MDM2 in a lung cancer cell line. This suppression of MDM2 resulted in increased radiosensitivity. The results support the hypothesis that MDM2 gene can be a candidate for radioresistance of A549 lung cancer cells, which may provide a potential molecular drug sensitizing the radioresistant cell A549. (authors)