Abstract 2617
Background
The high prevalence and poor prognosis of prostate cancer provides a strong rationale for developing new treatment strategies. Reovirus, a double-stranded RNA virus, preferentially kills a variety of cancer cells including those of prostate, breast and brain and have been studied in multiple clinical trials. In this study, we examine the oncolytic activity of reovirus and its potential as a therapeutic agent for human prostate cancer cell lines, with particular focus on the highly metastatic patient’s derived cell.
Methods
We used hormone-sensitive LNCaP cells, hormone-insensitive 22Rv1 cells, and castration resistant prostate cancer (CRPC) patient-derived primary cells. We analyzed in vitro anti-cancer effect of reovirus using real-time quantitative reverse transcription-PCR, western blotting, annexin V/propidium iodide assay and CellTiter Glo® luminescent assay. The murine TRAMP-C1 syngeneic and human 22Rv1 and patient-derived xenograft model was employed to evaluate in vivo efficacy. Statistical evaluation of the results was performed by one-way ANOVA.
Results
Reovirus significantly reduced cell viability in both androgen-sensitive LNCaP and androgen-insensitive 22Rv1 cells. The apoptosis induced by reovirus was associated with cleavage of caspase 3 and poly (ADP-ribose) polymerase (PARP) and increased annexin V-positive cells. Reovirus reduced expression of AR, AR splice variant 7 (AR-V7) and prostate specific antigen (PSA) in LNCaP and 22Rv1 cells. The treatment of reovirus inhibited the growth of TRAMP-C1, 22Rv1 and CRPC mouse model in vivo.
Conclusions
Taken together, our results show that reovirus has a strong anti-tumor effect in prostate cancer cells including CRPC in vitro and in vivo. It can be a promising virus-associated agent in the anticancer treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2018R1D1A1B01040663).
Disclosure
All authors have declared no conflicts of interest.
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