Loss of Ras association domain family
protein 1
isoform A (RASSF1A) expression is associated with the development of a variety of human
cancers and the expression of
carcinoembryonic antigen (CEA) frequently occurs in
gastric cancer. This study investigated the effects of RASSF1A expression restoration using a
hypoxia-inducible CEA promoter-driven vector on xenograft
tumor growth in nude mice and on the in-vitro regulation of
gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA
mRNA and
protein was much higher in
gastric cancer SGC7901 cells than in a second
gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited
gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed
matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced
gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a
hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of
gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced
gastric cancer.