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2015 ; 22
(10
): 793-801
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Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of
gastric cancer cells in vitro and in vivo
#MMPMID26005859
Zhou PH
; Zheng JB
; Wei GB
; Wang XL
; Wang W
; Chen NZ
; Yu JH
; Yao JF
; Wang H
; Lu SY
; Sun XJ
Gene Ther
2015[Oct]; 22
(10
): 793-801
PMID26005859
show ga
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.