[Inhibitory effect of 5-Aza-2'-deoxycytidine on human nasopharyngeal carcinoma xenograft in nude mice].
OBJECTIVE
5-Aza-2'-deoxycytidine (5-Aza-CdR) is an inhibitor of DNA methyltransferase; it may reactivate methylated antioncogene, therefore, inhibit the growth of cancer cells. This study was to observe the inhibitory effect of 5-Aza-CdR on the growth of human nasopharyngeal carcinoma (NPC) cells and xenografts in nude mice, explore the possible mechanisms, and search for new treatment target of NPC.


METHODS
NPC cell line CNE cells were treated with 5-Aza-CdR; the methylation status of death-associated protein kinase (DAPK) gene was evaluated by methylation-specific polymerase chain reaction (PCR). The model of human NPC xenograft in nude mice was constructed and treated with 5-Aza-CdR; the xenograft growth in nude mice was observed, and the mRNA and protein expression of DAPK was detected by reverse transcription-PCR (RT-PCR) and immunohistochemistry.


RESULTS
No expression of DAPK mRNA was found in CNE cells and the xenografts in nude mice without treatment of 5-Aza-CdR. After treatment, the expression of DAPK mRNA in CNE cells and the xenografts was increased along with the increasing concentration of 5-Aza-CdR; the growth of CNE cells and the xenografts in nude mice were obviously inhibited, and the methylated DAPK gene was reactivated. Four weeks after treatment, no significant difference was found in body weight of nude mice between 5-Aza-CdR group and control group [(22.35+/-2.02) g vs. (21.68+/-2.14) g, t=0.011, P>0.05]; the volume of xenografts was significantly smaller in 5-Aza-CdR group than in control group [(195.32+/-27.57) mm(3) vs. (343.67+/-23.08) mm(3), t=10.11, P<0.01].


CONCLUSIONS
5-Aza-CdR may reactivate antioncogene silenced by de novo methylation, therefore, inhibit the growth of CNE cells in vivo and in vitro.
Zhang
Song
S
Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, P. R. China.
Kong
Wei-Jia
WJ
Wang
Yan-Jun
YJ
Han
Yue-Chen
YC
Zhang
Dan
D
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D064550:Death-Associated Protein Kinases; D000077209:Decitabine; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D000077209:Decitabine; D015254:DNA Modification Methylases; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001374:Azacitidine