Bacterial RNA virus MS2 exposure increases the expression of cancer progression genes in the LNCaP prostate cancer cell line

Oncol Lett. 2023 Jan 17;25(2):86. doi: 10.3892/ol.2023.13672. eCollection 2023 Feb.

Abstract

Bacteriophages effectively counteract diverse bacterial infections, and their ability to treat most types of cancer has been explored using phage engineering or phage-virus hybrid platforms. In the present study, it was demonstrated that the bacteriophage MS2 can affect the expression of genes associated with the proliferation and survival of LNCaP prostate epithelial cells. LNCaP cells were exposed to bacteriophage MS2 at a concentration of 1×107 plaque forming units/ml for 24-48 h. After exposure, various cellular parameters, including cell viability, morphology, and changes in gene expression, were examined. MS2 affected cell viability adversely, reducing viability by 25% in the first 4 h of treatment; however, cell viability recovered within 24-48 h. Similarly, the AKT, androgen receptor, integrin α5, integrin β1, MAPK1, MAPK3, STAT3, and peroxisome proliferator-activated receptor-γ coactivator 1α genes, which are involved in various normal cellular processes and tumor progression, were significantly upregulated, whereas the expression levels of HSP90, ITGB5, ITGB3, HSP27, ITGAV, and PI3K genes were unchanged. Therefore, based on viability and gene expression changes, bacteriophage MS2 severely impaired LNCaP cells by reducing anchorage-dependent survival and androgen signaling. A caveolin-mediated endocytosis mechanism for MS2-mediated signaling in prostate cancer cells was proposed based on reports involving bacteriophages T4, M13, and MS2, and their interactions with LNCaP and PC3 cell lines.

Keywords: MS2; androgen receptor; bacteriophage; gene expression; integrin.

Grants and funding

Funding was received from the National Council for Scientific and Technological Development (CNPq; grant nos. 465699/2014-6 and 310805/2018-0) and São Paulo Research Foundation (FAPESP; grant nos. 2014/50938-8 and 2019/19644-1). The present study was also carried out with the support of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES; finance code 001; grant no. 963-14-2).