Apoptosis of murine melanoma cells induced by heavy-ion radiation combined with Tp53 gene transfer.
OBJECTIVE
To investigate the effect of exogenous wild type p53 (Tp53) on murine melanoma B16 cell apoptosis induced by carbon-ion beam (C-beam) irradiation.


METHODS
The murine cell line B16, which has wild-type Tp53 gene status was studied, as well as B16 cells transfected with an adenoviral vector containing the wild-type Tp53 gene (B16/Tp53). Cells were irradiated with C-beam and assayed for cell survival (colony-forming assay), cellular morphology (acridine orange assay), the frequency of apoptotic cells (fluorescence microscopy) and protein expression (Western blot analysis).


RESULTS
The radiosensitivity of B16/Tp53 cells was significantly higher than that of B16 cells. In contrast with Tp53 transfer alone, the combination of C-beam with Tp53 transfer induced a higher proportion of apoptotic cells and micronuclei. After C-beam irradiation, there was no significant increased expression of the cyclin-dependent kinase inhibitor p21 and Tp53 in B16/Tp53 cells compared to B16 cells, but a decreased expression of murine double minute-2 (Mdm2) was observed.


CONCLUSIONS
The results of this study suggest the potential application of C-beam combined with Tp53 in the treatment of melanoma in human patients.
Duan
Xin
X
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu Province, China.
Zhang
Hong
H
Liu
Bing
B
Li
Xiao-Da
XD
Gao
Qing-Xiang
QX
Wu
Zheng-Hua
ZH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002244:Carbon; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005822:Genetic Vectors; D020450:Heavy Ions; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D011839:Radiation, Ionizing; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D002244:Carbon; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2