Knock-down of methylenetetrahydrofolate reductase reduces gastric cancer cell survival: An in vitro study

被引:7
|
作者
Sun, Dan-Feng [1 ]
Weng, Yu-Rong [1 ]
Chen, Ying-Xuan [1 ]
Lu, Rong [1 ]
Wang, Xia [1 ]
Fang, Jing-Yuan [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Inst Digest Dis, Shanghai 200001, Peoples R China
关键词
Methionine dependence; Methylenetetrahydrofolate reductase; Gastric cancer; RNA interference;
D O I
10.1016/j.cellbi.2008.03.018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The present study aimed to investigate the effect of knocking-down methylenetetrahydrofolate reductase ( MTHFR) on the survival of the human gastric cancer cell line MKN45. Antisense and small interfering RNA ( siRNA) plasmids were used to target MTHFR in MKN45. Meanwhile, we also constructed a wild-type MTHFR plasmid to assess the effect of over-expression of this protein on cell viability. The knock-down of MTHFR decreased cell survival by approximately 30% compared to the control and resulted in cell cycle arrest at the G2 phase. These cells also had lower levels of c-myc compared to control cells, while over-expression of MTHFR increased cell proliferation and induced the down-regulation of p21(WAF1) and hMLH1. Inhibiting MTHFR with either antisense or siRNA decreases the viability of methionine-dependent transformed gastric cancer cells and suggests that MTHFR inhibition may be a novel anticancer approach. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:879 / 887
页数:9
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