Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene
Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter
#MMPMID26053394
Rama AR
; Hernandez R
; Perazzoli G
; Burgos M
; Melguizo C
; Vélez C
; Prados J
Int J Mol Sci
2015[Jun]; 16
(6
): 12601-15
PMID26053394
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Colorectal cancer is one of the most prevalent cancers in the world. Patients in
advanced stages often develop metastases that require chemotherapy and usually
show a poor response, have a low survival rate and develop considerable toxicity
with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to
destroy the tumor without affecting normal host tissue. The bacteriophage E gene
has demonstrated significant antitumor activity in several cancers, but without
any tumor-specific activity. The use of tumor-specific promoters may help to
direct the expression of therapeutic genes so they act against specific cancer
cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene
expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth
inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer
cells in comparison to normal human CCD18co colon cells, which have practically
undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors
induced using MC-38 cells showed a significant decrease in tumor volume after
pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These
results suggest that the CEA promoter is an excellent candidate for directing E
gene expression specifically toward colon cancer cells.
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