Adenovirus vector-mediated upregulation of spermidine /spermine N1-acetyltransferase impairs human gastric cancer growth in vitro and in vivo.
Spermidine/spermine N(1)-acetyltransferase (SSAT) is the rate-limiting step in polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of upregulated and downregulated SSAT on gastric cancer cells. We found that upregulated SSAT could inhibit the growth of MGC803 and SGC7901 cells, whereas adverse results were found with downregulated SSAT. We further analyzed cell cycle profiles and the expression levels of the major cell cycle regulatory proteins of S phase. The results showed that the growth inhibition was caused by S phase arrest. Ad-SSAT suppressed the expression of cyclin A and nuclear factor E2F1 in MGC803 and SGC7901 cells. We observed the E2F promoter activity caused by Ad-SSAT using a reporter gene assay. We also investigated the antitumorigenicity of upregulated SSAT by Ad-SSAT using a SGC7901 xenograft model in nude mice. Our results suggest that the upregulation of SSAT by Ad-SSAT infection inhibited the growth of gastric cancer in vitro and in vivo. Ad-SSAT arrested gastric cancer cells in S phase, which was mediated through downregulation of the cyclin A-E2F signaling pathway.
Liu
Bin
B
Institute of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, 250012, PR China.
Sun
Hui
H
Wang
Wei
W
Li
Wei
W
Yan
Yun-Fei
YF
Chen
Shi-Min
SM
Yang
Ya-Pei
YP
Xu
Chun-Xiao
CX
Xin
Jia-Xuan
JX
Liu
Xian-Xi
XX
D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015317:Biogenic Polyamines / Q000032:analysis; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000037:antagonists & inhibitors; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016196:S Phase; D013274:Stomach Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D015317:Biogenic Polyamines; D019925:Cyclin A; D050687:E2F1 Transcription Factor; D000099228:Diamine N-Acetyltransferase
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