Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells

  • Authors:
    • Jose Prados
    • Consolacion Melguizo
    • Ana Rama
    • Raul Ortiz
    • Houria Boulaiz
    • Fernando Rodriguez-Serrano
    • Octavio Caba
    • Jose Juan Rodriguez-Herva
    • Juan Luis Ramos
    • Antonia Aranega
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.121
  • Pages: 121-127
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Abstract

The low efficiency of conventional therapies in achieving long-term survival of lung cancer patients calls for development of novel options. The potential use of combined gene therapy is under intensive study. One approach uses the expression of genes encoding cytotoxic proteins that affect cellular viability. The gef gene from E. coli, identified as a member of a gene family encoding homologous cell-killing functions, encodes for a membrane protein with a toxic domain which leads to a decrease in the rate of tumour cell growth. To improve the antitumoral effect of the paclitaxel in lung cancer cells, we investigated a combined suicide gene therapy using this drug and gef gene in vitro, using A-549 lung cancer cells in culture and forming multicellular tumour spheroids (MTS). Our results showed that gef expression in A-549 cells led to an ultrastructural changes, including dilated mitochondria with clear matrices and disrupted cristae and cell surface alterations such as reduction in length and number of microvilli and cytoplasmic membrane evaginations. The use of paclitaxel in A-549 lung cancer cells transfected with gef gene enhanced the chemotherapeutic effect of this drug. Volume analyses showed an 87.4% decrease in the A-549 MTS growth after 96 h in comparison with control MTS. This inhibition was greater than that obtained using the gene therapy or chemotherapy alone. In conclusion, gef gene has a cytotoxic effect in lung cancer cells and enhances cell growth inhibition when used with paclitaxel. These results indicate that this combined therapy may be of potential therapeutic value in lung cancer.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Prados J, Melguizo C, Rama A, Ortiz R, Boulaiz H, Rodriguez-Serrano F, Caba O, Rodriguez-Herva JJ, Ramos JL, Aranega A, Aranega A, et al: Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells. Int J Oncol 33: 121-127, 2008
APA
Prados, J., Melguizo, C., Rama, A., Ortiz, R., Boulaiz, H., Rodriguez-Serrano, F. ... Aranega, A. (2008). Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells. International Journal of Oncology, 33, 121-127. https://doi.org/10.3892/ijo.33.1.121
MLA
Prados, J., Melguizo, C., Rama, A., Ortiz, R., Boulaiz, H., Rodriguez-Serrano, F., Caba, O., Rodriguez-Herva, J. J., Ramos, J. L., Aranega, A."Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells". International Journal of Oncology 33.1 (2008): 121-127.
Chicago
Prados, J., Melguizo, C., Rama, A., Ortiz, R., Boulaiz, H., Rodriguez-Serrano, F., Caba, O., Rodriguez-Herva, J. J., Ramos, J. L., Aranega, A."Combined therapy using suicide gef gene and paclitaxel enhances growth inhibition of multicellular tumour spheroids of A-549 human lung cancer cells". International Journal of Oncology 33, no. 1 (2008): 121-127. https://doi.org/10.3892/ijo.33.1.121