hokd as a potential tool for directed cancer gene therapy

Y Jiménez Martínez(2) A Arroyo Jiménez(2) C Griñan(2) J Peña(2) J Jimenez(2) E Carrillo(2) J Marchal(2) H Boulaiz(2)

1:Radboud University MC; 2:Universidad de Granada

Owing to the difficult cancer staging, diagnostic, prognostic and treatment, researches in new therapies, more effective and with low side effects, are increasing. Currently, one of the most interesting therapies is suicide gene therapy. In the direct way, it consists in the introduction of a gene responsible of the production of a toxin, which will destroy the cell from his inside. In the present manuscript our purpose was to investigate the antitumor efficacy of hokD gene under the control of different promoters (induced or tumor-specific promoters) in cervix (HeLa) and breast (MCF-7) cancer cells. Experiments were conducted in vitro in 2D and 3D culture model and in vivo using NOD SCID mice. Our results showed that hokD gene expression under the control of tumor-specific promoter causes a drastic inhibition of HeLa and MCF-7 cells proliferation in vitro in both 2D and 3D models. Moreover, an important decrease on cell viability was observed by ATPlite analysis. Furthermore, hokD gene induced a severe loss of proliferation in vivo without any side effects in our animal model. Taking into account our results, this combination of gene and promoter could be a great option in future breast and cervical cancer therapies.