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Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.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.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of Ki-67 expression in mice bearing subcutaneous MC-38 tumors treated with pCEA-E. (A) Images of Ki-67 expression (green) and cell nuclei stained with DAPI (blue). Original magnification: 10×; and (B) Ki-67 histogram protein expression profiles. Ki-67 expression was lower in the pCEA-E-treated group than in the pCEA-LacZ and control groups (* p < 0.05).
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ijms-16-12601-f006: Immunohistochemical staining of Ki-67 expression in mice bearing subcutaneous MC-38 tumors treated with pCEA-E. (A) Images of Ki-67 expression (green) and cell nuclei stained with DAPI (blue). Original magnification: 10×; and (B) Ki-67 histogram protein expression profiles. Ki-67 expression was lower in the pCEA-E-treated group than in the pCEA-LacZ and control groups (* p < 0.05).

Mentions: To determine the effect of pCEA-E on cell proliferation and apoptosis, we examined Ki-67 expression using immunohistochemical staining and detected apoptotic cells using the TUNEL assay. Our results showed that Ki-67 expression significantly decreased (55.4% of expression relative to the control tissue) in tumors that received pCEA-E treatment, suggesting significant inhibition of cell proliferation (p < 0.05) (Figure 6).


Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

Rama AR, Hernandez R, Perazzoli G, Burgos M, Melguizo C, Vélez C, Prados J - Int J Mol Sci (2015)

Immunohistochemical staining of Ki-67 expression in mice bearing subcutaneous MC-38 tumors treated with pCEA-E. (A) Images of Ki-67 expression (green) and cell nuclei stained with DAPI (blue). Original magnification: 10×; and (B) Ki-67 histogram protein expression profiles. Ki-67 expression was lower in the pCEA-E-treated group than in the pCEA-LacZ and control groups (* p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490463&req=5

ijms-16-12601-f006: Immunohistochemical staining of Ki-67 expression in mice bearing subcutaneous MC-38 tumors treated with pCEA-E. (A) Images of Ki-67 expression (green) and cell nuclei stained with DAPI (blue). Original magnification: 10×; and (B) Ki-67 histogram protein expression profiles. Ki-67 expression was lower in the pCEA-E-treated group than in the pCEA-LacZ and control groups (* p < 0.05).
Mentions: To determine the effect of pCEA-E on cell proliferation and apoptosis, we examined Ki-67 expression using immunohistochemical staining and detected apoptotic cells using the TUNEL assay. Our results showed that Ki-67 expression significantly decreased (55.4% of expression relative to the control tissue) in tumors that received pCEA-E treatment, suggesting significant inhibition of cell proliferation (p < 0.05) (Figure 6).

Bottom Line: The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity.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.These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Science, University of Jaén, Jaén 23071, Spain. arama@ujaen.es.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus