Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium io
n channel family, and its site-directed active mutant (MDEG-G430F) induces
massive Na+ influx into cells, leading to cell ballooning and cell bursting
. We attempted a novel therapeutic approach for gastric cancers by transfer
ring MDEG-G430F into cancer cells using tumor-specific promoters. In carcin
oembryonic antigen (CEA)-producing gastric cancer cells, the level of cell
death observed when MDEG-G430F was used with a CEA promoter was similar to
that observed when using a potent nonspecific promoter such as the cytomega
lovirus promoter. in an in vivo study, fusogenic liposome complexes contain
ing MDEG-G430F driven by the CEA promoter were injected intraperitoneally i
nto CEA-producing gastric cancer cells in a mouse peritoneal dissemination
model. Although all 15 of the control mice were dead by 50 days postinocula
tion, 13 of the 15 mice treated with MDEG-G430F survived. These results ind
icate that transferring MDEG-G430F into cancer tissues using tumor-specific
promoters can achieve striking and selective cancer cell death irrespectiv
e of the transcriptional efficiency of the promoters used in vivo, and sugg
est that this approach is a promising new strategy for cancer gene therapy.