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Published on: November 19, 2019
Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate
Swapnil Ganesh Sanmukh1, Nilton José Dos Santos1,2, Caroline Nascimento Barquilha1,2
1Laboratory of Extracellular Matrix Biology, Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, Sao Paulo State University (UNESP), Botucatu 18618-689, SP, Brazil.
Abstract:
Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 105 pfu/mL, 1 × 106 pfu/mL, and 1 × 107 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K were significantly up-regulated, whilst the genes AR, HSPB1, ITGAV, and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.
Insights
Bacteriophages M13 and T4 alter gene expression in prostate cancer cells, affecting survival and androgen signaling pathways. This suggests phage therapy could enhance treatments targeting the PI3K/AKT pathway.
Area of Science:
- Oncology
- Microbiology
- Molecular Biology
Background:
- Bacteriophages (phages) are explored as therapeutic agents for diseases, including cancer, acting as naked viruses or carriers of antitumor molecules.
- Prostate cancer (PCa) remains a significant health concern, with androgen signaling playing a crucial role in its development and progression.
Purpose of the Study:
- To investigate the effects of bacteriophages M13 and T4 on gene expression in LNCaP cells, a model for androgen-responsive prostate cancer.
- To determine if phage interaction with cancer cells influences genes involved in cell adhesion, growth, and survival.
Main Methods:
- LNCaP cells were exposed to bacteriophages M13 and T4 at varying concentrations (1x10^5 to 1x10^7 pfu/mL) for different durations (24, 48, 72 hours).
- Assessed cellular morphology, cell viability (MTT assay), and analyzed gene expression changes using molecular techniques.
Main Results:
- Phage treatment did not alter LNCaP cell morphology but reduced cell viability.
- Significant upregulation of genes including AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K was observed.
- Downregulation of genes such as AR, HSPB1, ITGAV, and PGC1A indicated modulation of androgen signaling and survival pathways.
Conclusions:
- Bacteriophages M13 and T4 interact with LNCaP cells, inducing significant gene expression changes.
- These changes are related to anchorage-dependent survival and androgen signaling pathways.
- Phage therapy holds potential for enhancing the efficacy of prostate cancer treatments, particularly those targeting the PI3K/AKT pathway.
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