[Enhancive effect of histone deacetylase inhibitor trichostatin a on transfection efficiency of adenovirus in ovarian carcinoma cell line A2780].
OBJECTIVE
The presence of Coxsackie and adenovirus receptor (CAR) on target cell surface is required for efficient adenovirus transfection; lack or down-regulated expression of CAR on cancer cells is the main cause of inefficiency of adenovirus-based gene therapy. This study was to evaluate enhancive effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on the transfection efficiency of adenovirus in ovarian carcinoma cell line A2780, and explore its possible application to adenovirus-based gene therapy.


METHODS
mRNA and protein levels of CAR on A2780 cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot before and after treatment of TSA. Transfection efficiency of adenovirus was valued by flow cytometry (FCM). In vitro antitumor effect of adenovirus/thymidine kinase (ADV/TK) was detected by MTT assay.


RESULTS
After treatment of TSA, mRNA and protein levels of CAR on A2780 cells were obviously increased. Transfection rates of adenovirus were (1.24+/-0.14)% in untreated group, (7.58+/-0.32)% in 5 nmol/L of TSA treated group, and (7.94+/-0.28)% in 100 nmol/L of TSA treated groups. In vitro antitumor effect of ADV/TK was 4-10 folds in TSA (5 or 100 nmol/L) treated groups compared with that in untreated group.


CONCLUSIONS
TSA could enhance transfection efficiency of adenovirus in ovarian carcinoma cells, and may be useful in gene therapy for ovarian carcinoma.
Chen
Gang
G
Molecular Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
Wang
Bei-Bei
BB
Li
Fu-Jun
FJ
Liu
De-Yan
DY
Zhou
Jian-Feng
JF
Lu
Yun-Ping
YP
Ma
Ding
D
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000235:genetics; D013937:Thymidine Kinase / Q000494:pharmacology; D014162:Transfection
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D011991:Receptors, Virus; C012589:trichostatin A; D013937:Thymidine Kinase