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.
Resources from the same session
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract