Non-viral suicide gene therapy in cervical, oral and pharyngeal carcinoma cells with CMV- and EEV-plasmids
© 2018 John Wiley & Sons, Ltd..
BACKGROUND: Cervical cancer is the third most common cause of cancer in women. The 5-year survival rate in oropharyngeal squamous cell carcinomas is approximately 50% and this rate has not improved in recent decades. These cancers are accessible to direct intervention. We examined the ability of a highly efficient non-viral vector, TransfeX (ATCC, Manassas, VA, USA), to deliver the suicide gene HSV-tk to cervical, oral and pharyngeal cancer cells and to induce cytotoxicity following the administration of the prodrug, ganciclovir.
METHODS: HeLa cervical carcinoma, HSC-3 and H357 oral squamous cell carcinoma and FaDu pharyngeal carcinoma cells were transfected with cytomegalovirus (CMV)- or enhanced episomal vector (EEV)-driven HSV-tk plasmids and treated with ganciclovir for 24-120 h. Cell viability was assessed by Alamar blue.
RESULTS: The viability of HeLa cells was reduced to only 30-40%, despite the very high levels of transgene expression. By contrast, the viability of HSC-3 cells was reduced to 10%, although transgene expression was 18-fold lower than that in HeLa cells. An approximately five-fold higher transgene expression was obtained with the EEV-plasmid than from the CMV-plasmid. Nevertheless, HeLa cell viability after suicide gene + ganciclovir treatment was reduced by only 35% compared to 70% with the CMV-plasmid. For HSC-3 cells, the reduction was 40% for the EEV- and 80% for the CMV-plasmid. The lower efficiency of transfection with the EEV-plasmid may explain the lower cytotoxicity.
CONCLUSIONS: TransfeX-mediated gene delivery to cervical, pharyngeal and oral cancer cells may be used for suicide gene therapy. The levels of transgene expression, however, do not translate directly to cytotoxicity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
The journal of gene medicine - 20(2018), 10-11 vom: 05. Okt., Seite e3054 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Düzgüneş, Nejat [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.09.2019 Date Revised 16.09.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/jgm.3054 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2018 John Wiley & Sons, Ltd. | ||
| 520 | |a BACKGROUND: Cervical cancer is the third most common cause of cancer in women. The 5-year survival rate in oropharyngeal squamous cell carcinomas is approximately 50% and this rate has not improved in recent decades. These cancers are accessible to direct intervention. We examined the ability of a highly efficient non-viral vector, TransfeX (ATCC, Manassas, VA, USA), to deliver the suicide gene HSV-tk to cervical, oral and pharyngeal cancer cells and to induce cytotoxicity following the administration of the prodrug, ganciclovir | ||
| 520 | |a METHODS: HeLa cervical carcinoma, HSC-3 and H357 oral squamous cell carcinoma and FaDu pharyngeal carcinoma cells were transfected with cytomegalovirus (CMV)- or enhanced episomal vector (EEV)-driven HSV-tk plasmids and treated with ganciclovir for 24-120 h. Cell viability was assessed by Alamar blue | ||
| 520 | |a RESULTS: The viability of HeLa cells was reduced to only 30-40%, despite the very high levels of transgene expression. By contrast, the viability of HSC-3 cells was reduced to 10%, although transgene expression was 18-fold lower than that in HeLa cells. An approximately five-fold higher transgene expression was obtained with the EEV-plasmid than from the CMV-plasmid. Nevertheless, HeLa cell viability after suicide gene + ganciclovir treatment was reduced by only 35% compared to 70% with the CMV-plasmid. For HSC-3 cells, the reduction was 40% for the EEV- and 80% for the CMV-plasmid. The lower efficiency of transfection with the EEV-plasmid may explain the lower cytotoxicity | ||
| 520 | |a CONCLUSIONS: TransfeX-mediated gene delivery to cervical, pharyngeal and oral cancer cells may be used for suicide gene therapy. The levels of transgene expression, however, do not translate directly to cytotoxicity | ||
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| 700 | 1 | |a Konopka, Krystyna |e verfasserin |4 aut | |
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