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

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.