[Apoptotic induction of human lung carcinoma A549 cells by DFMO through Fas/FasL pathway].
OBJECTIVE
Fas/FasL pathway play an important role in cell apoptosis. To investigate the role of Fas/FasL system in polyamine biosynthesis inhibition and malignant phenotype reversion of carcinoma cells, we examined the effect of DFMO (alpha-difluoromethylornithine), an inhibitor of polyamine biosynthesis, on cell growth and apoptosis of A549 cells, and their association with human lung carcinoma-associated antigen, ras P21 protein, and Fas/FasL.


METHODS
MTT assay,flow cytometry,and DNA fragmentation analysis were used to determine cell growth and apoptosis,respectively. The gene and protein expression were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively.


RESULTS
DFMO could inhibit the growth of A549 cells and induce their apoptosis, meanwhile the cells in G(1) phase were increased with (61.0+/-2.08)%, the cells in S phase were decreased with (21.2+/-0.88)%, and DNA ladder were observed. Simultaneously, the expression of human lung carcinoma-associated antigen and ras P21 protein were downregulated, but Fas mRNA and protein expression were upregulated.


CONCLUSIONS
DFMO induce apoptosis of human lung carcinoma A549 cells through Fas/FasL pathway. It might be correlated with the expression of human lung carcinoma-associated antigen and ras P21 protein.
Xiang
Qing
Q
Department of Oncology and Molecular Biology, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, PR China. xiang_qing@hotmail.com
Fan
Mu-Zhen
MZ
Xu
Bo
B
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology*; D053222:Fas Ligand Protein; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D000518:Eflornithine