ArticleMolecular vision2012
ATRA enhances the bystander effect of suicide gene therapy driven by the specific promoter LEP 503 in human lens epithelial cells.
Article in Molecular vision, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells.Oncology letters · 2017Article
- Dioscin augments HSV-tk-mediated suicide gene therapy for melanoma by promoting connexin-based intercellular communication.Oncotarget · 2017Article
- The Polymorphisms with Cataract Susceptibility Impair the EPHA2 Receptor Stability and Its Cytoprotective Function.Journal of ophthalmology · 2015Article
- Vesicular Stomatitis Virus G Glycoprotein and ATRA Enhanced Bystander Killing of Chemoresistant Leukemic Cells by Herpes Simplex Virus Thymidine Kinase/Ganciclovir.Biomolecules & therapeutics · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo establish a novel, targeted lentivirus-mediated LEP503-HSV-tk/GCV suicide gene therapy system combined with all trans-retinoic acid (ATRA) for the inhibition of human lens epithelial cell (HLEC) proliferation and treatment of posterior capsular opacification (PCO) after cataract surgery; to estimate the enhancement of the bystander effect by ATRA; and to explore the role of Connexin43 (Cx43) mediated gap junctional intercellular communication (GJIC) in the bystander effect of the HSV-K/GCV system.
methodsA Lenti-LEP503-HSV-tk-EGFP vector was generated by cloning the lens-specific promoter LEP503 (lens specific promoter 503) from genomic DNA of HLECs by PCR. The vector was then inserted into the promoter-less vector from lentivirus-based (CMV)-HSV-tk-EGFP. The expressional specificity of the LEP503 promoter was assessed by investigating the expression of EGFP (enhanced green fluorescent protein) and HSV-tk (herpes simplex virus thymidine kinase) mRNA, both driven by Lenti-LEP503-HSV-tk-EGFP vector, by fluorescence microscopy, RT-PCR, flow cytometry, and western blot assays in HLECs, human adult retinal pigment epithelium cells (RPECs), human adult skin fibroblast cells (ASFCs), and Hela cells. Morphological changes were observed by fluorescence microscopy and cell viability was determined using the Cell Counting kit-8 Cell Proliferation (CCK-8) and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays after Lenti-LEP503-HSV-tk/GCV system combined with ATRA treatment on HLECs. Flow cytometry, DNA fragmentation, and western blot assays were employed to analyze the mechanisms of bystander effects.
resultsThe promoter LEP503-mediated HSV-tk was specifically expressed in HLECs, and ATRA dose-dependently strengthened the bystander effect following LEP503-mediated HSV-tk/GCV gene therapy against lens cells by upregulating the expression of the gap junction protein Cx43.
conclusionsThe Lenti-LEP503-HSV-tk/GCV suicide gene therapy system, combined with ATRA as an adjuvant, may be a feasible supplementary method for PCO treatment that targets residual lens cells.
Indexed as
Identifiers
22876133PMC3413421W2124257943What OpenQuestion holds
Registered trials
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