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Specific driving of the suicide E gene by the CEA promoter enhances the effects of paclitaxel in lung cancer

Cancer Gene Therapy volume 27, pages 657–668 (2020)Cite this article

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A Correction to this article was published on 06 February 2020

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Abstract

Classical chemotherapy for lung cancer needs new strategies to enhance its antitumor effect. The cytotoxicity, nonspecificity, and low bioavailability of paclitaxel (PTX) limits their use in this type of cancer. Suicide gene therapy using tumor-specific promoters may increase treatment effectiveness. We used carcinoembryonic antigen (CEA) as a tumor-specific promoter to drive the bacteriophage E gene (pCEA-E) towards lung cancer cells (A-549 human and LL2 mice cell lines) but not normal lung cells (L132 human embryonic lung cell line), in association with PTX as a combined treatment. The study was carried out using cell cultures, tumor spheroid models (MTS), subcutaneous induced tumors and lung cancer stem cells (CSCs). pCEA-E induced significant inhibition of A-549 and LL2 cell proliferation in comparison to L132 cells, which have lower CEA expression levels. Moreover, pCEA-E induced an important decrease in volume growth of A-549 and LL2 MTS producing intense apoptosis, in comparison to L132 MTS. In addition, pCEA-E enhanced the antitumor effects of PTX when combined, showing a synergistic effect. This effect was also observed in A-549 CSCs, which have been related to the recurrence of cancer. The in vivo study corroborated the effectiveness of the pCEA-E-PTX combined therapy, inducing a greater decrease in tumor volume compared to PTX and pCEA-E alone. Our results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically towards lung cancer cells, and may be used to enhance the effectiveness of PTX against this type of tumor.

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  • 06 February 2020

    The original version of this Article contained an error in the spelling of the author Ana Rosa Rama Ballesteros, which was incorrectly given as Ana Rosa Rama. This has now been corrected in both the PDF and HTML versions of the Article.

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Funding

This work was funded by Consejería de Salud de la Junta de Andalucía (project PI-0476-2016 and PI-0102-2017) and by Granada University (project PP2015-13 and financial Groups 09/112016).

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Authors and Affiliations

  1. Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada, Spain

    Ana Rosa Rama Ballesteros, Rosa Hernández, Gloria Perazzoli, Laura Cabeza, Consolación Melguizo, Celia Vélez & Jose Prados

  2. Department of Health Science, University of Jaén, Jaén, Spain

    Ana Rosa Rama Ballesteros

  3. Biosanitary Institute of Granada (ibs. GRANADA), SAS-Universidad de Granada, Granada, Spain

    Rosa Hernández, Gloria Perazzoli, Laura Cabeza, Consolación Melguizo, Celia Vélez & Jose Prados

  4. Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain

    Rosa Hernández, Laura Cabeza, Consolación Melguizo, Celia Vélez & Jose Prados

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  1. Ana Rosa Rama Ballesteros
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  2. Rosa Hernández
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Correspondence to Ana Rosa Rama Ballesteros.

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Rama Ballesteros, A., Hernández, R., Perazzoli, G. et al. Specific driving of the suicide E gene by the CEA promoter enhances the effects of paclitaxel in lung cancer. Cancer Gene Ther 27, 657–668 (2020). https://doi.org/10.1038/s41417-019-0137-3

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