دورية أكاديمية
Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model
العنوان: | Retroviral Replicating Vectors Mediated Prodrug Activator Gene Therapy in a Gastric Cancer Model |
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المؤلفون: | Hiroaki Fujino, Emiko Sonoda-Fukuda, Lisa Isoda, Ayane Kawabe, Toru Takarada, Noriyuki Kasahara, Shuji Kubo |
المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 19, p 14823 (2023) |
بيانات النشر: | MDPI AG, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | gastric cancer, retroviral replicating vectors, prodrug activator gene therapy, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/24/19/14823; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms241914823 |
URL الوصول: | https://doaj.org/article/edc6fa83d30d40309e2bd3a79b6f88ca |
رقم الأكسشن: | edsdoj.6fa83d30d40309e2bd3a79b6f88ca |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
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DOI: | 10.3390/ijms241914823 |