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10.3390/ijms241914823
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Article

Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model

by
Hiroaki Fujino
1,2,
Emiko Sonoda-Fukuda
1,
Lisa Isoda
1,2,
Ayane Kawabe
1,2,
Toru Takarada
1,3,
Noriyuki Kasahara
4 and
Shuji Kubo
1,*
1
Laboratory of Molecular and Genetic Therapeutics, Institute of Advanced Medical Science, Hyogo Medical University, Hyogo 663-8501, Japan
2
Departments of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Hyogo 669-1330, Japan
3
Laboratory of Functional Molecular Chemistry, Kobe Pharmaceutical University, Hyogo 658-8558, Japan
4
Departments of Neurological Surgery and Radiation Oncology, University of California, San Francisco, CA 94143, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(19), 14823; https://doi.org/10.3390/ijms241914823
Submission received: 4 August 2023 / Revised: 29 September 2023 / Accepted: 29 September 2023 / Published: 2 October 2023
(This article belongs to the Section Molecular Oncology)
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Abstract

Retroviral replicating vectors (RRVs) selectively replicate and can specifically introduce prodrug-activating genes into tumor cells, whereby subsequent prodrug administration induces the death of the infected tumor cells. We assessed the ability of two distinct RRVs generated from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), which infect cells via type-III sodium-dependent phosphate transporters, PiT-2 and PiT-1, respectively, to infect human gastric cancer (GC) cells. A quantitative RT-PCR showed that all tested GC cell lines had higher expression levels of PiT-2 than PiT-1. Accordingly, AMLV, encoding a green fluorescent protein gene, infected and replicated more efficiently than GALV in most GC cell lines, whereas both RRVs had a low infection rate in human fibroblasts. RRV encoding a cytosine deaminase prodrug activator gene, which converts the prodrug 5-flucytosine (5-FC) to the active drug 5-fluorouracil, showed that AMLV promoted superior 5-FC-induced cytotoxicity compared with GALV, which correlated with the viral receptor expression level and viral spread. In MKN-74 subcutaneous xenograft models, AMLV had significant antitumor effects compared with GALV. Furthermore, in the MKN-74 recurrent tumor model in which 5-FC was discontinued, the resumption of 5-FC administration reduced the tumor volume. Thus, RRV-mediated prodrug activator gene therapy might be beneficial for treating human GC.
Keywords: gastric cancer; retroviral replicating vectors; prodrug activator gene therapy gastric cancer; retroviral replicating vectors; prodrug activator gene therapy

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MDPI and ACS Style

Fujino, H.; Sonoda-Fukuda, E.; Isoda, L.; Kawabe, A.; Takarada, T.; Kasahara, N.; Kubo, S. Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model. Int. J. Mol. Sci. 2023, 24, 14823. https://doi.org/10.3390/ijms241914823

AMA Style

Fujino H, Sonoda-Fukuda E, Isoda L, Kawabe A, Takarada T, Kasahara N, Kubo S. Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model. International Journal of Molecular Sciences. 2023; 24(19):14823. https://doi.org/10.3390/ijms241914823

Chicago/Turabian Style

Fujino, Hiroaki, Emiko Sonoda-Fukuda, Lisa Isoda, Ayane Kawabe, Toru Takarada, Noriyuki Kasahara, and Shuji Kubo. 2023. "Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model" International Journal of Molecular Sciences 24, no. 19: 14823. https://doi.org/10.3390/ijms241914823

APA Style

Fujino, H., Sonoda-Fukuda, E., Isoda, L., Kawabe, A., Takarada, T., Kasahara, N., & Kubo, S. (2023). Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model. International Journal of Molecular Sciences, 24(19), 14823. https://doi.org/10.3390/ijms241914823

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