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
3264 - A novel preclinical model of RAF-independent MEK1 mutant tumors and its treatment with novel ATP competitive MEK inhibitor
Presenter: Luca Hegedus
Session: Poster Display session 3
Resources:
Abstract
4918 - HER2 inhibition in Aggressive Squamous Cell Carcinomas driven by a common MET Sema Domain Polymorphism
Presenter: Nur Afiqah Mohamed Salleh
Session: Poster Display session 3
Resources:
Abstract
2426 - ADAM9 as a target for lung cancer treatment
Presenter: Yuh-pyng Sher
Session: Poster Display session 3
Resources:
Abstract
5537 - Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer
Presenter: Marta Perez Hernandez
Session: Poster Display session 3
Resources:
Abstract
1597 - Discovery of Clinical Candidate DBPR112, a Furanopyrimidine-based Epidermal Growth Factor Receptor Inhibitor for the Treatment of Non-Small Cell Lung Cancer
Presenter: Hsing-pang Hsieh
Session: Poster Display session 3
Resources:
Abstract
3543 - Molecular characteristics in lung squamous cell carcinomas dependent on TP53 status – putative targets
Presenter: Vilde Haakensen
Session: Poster Display session 3
Resources:
Abstract
4111 - Comparison of molecular profiles between primary tumour and matched metastasis in non-small cell lung cancer
Presenter: Asuka Kawachi
Session: Poster Display session 3
Resources:
Abstract
4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer
Presenter: Giuseppe Curigliano
Session: Poster Display session 3
Resources:
Abstract
2501 - Triple MET/SRC/PIM inhibition in MET addicted tumors
Presenter: Ilaria Attili
Session: Poster Display session 3
Resources:
Abstract
5655 - Bioactivation of napabucasin triggers reactive oxygen species–mediated cancer cell death
Presenter: Fieke Froeling
Session: Poster Display session 3
Resources:
Abstract