Abstract
BackgroundConditionally replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. However, the traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can’t be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5.MethodsWe utilized Ad5/F11p containing the chimeric fiber gene encoding the Ad5 fiber tail domain and Ad11p fiber shaft and knob domains to construct bladder cancer-specific chimeric type viruses Ad5/F11p-PSCAE-UPII-E1A, which can infect bladder cancer cells mediated by CD46 molecule. We carried out series of experiments in vitro to research anti-tumor effect of Ad5/F11p-PSCAE-UPII-E1A and the interaction in combination with cisplatin.ResultsThe results demonstrated Ad5/F11p-PSCAE-UPII-E1A could infect bladder cancer cells (T24, EJ and 5637) in a CAR-independent way, and exert anti-tumor effect by blocking the cancer cells in G1 phase and inducing apoptosis. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin enhanced the anti-proliferative effect and increased the number of apoptotic cells compared with viruses or cisplatin alone. Ad5/F11p-PSCAE-UPII-E1A plus cisplatin could upregulate the proteins expression of p53, Bax, and cleaved caspase-3, and downregulated Bcl-2 protein expression in T24, EJ and 5637 cells.ConclusionWe constructed a bladder cancer-specific oncolytic adenovirus and provided new combination treatment strategies for bladder cancer.
Highlights
Replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects
prostate stem cell antigen enhancer (PSCAE) gene, UPII gene, and Early adenoviral genes (E1A) gene express in adenovirus of serotype 5 (Ad5)/F11pPSCAE-UPII-E1A was identified by polymerase chain reaction (PCR)
Our results showed Ad5/F11p-PSCAE-UPII-E1A was effective for bladder cancer cells and its infectivity were not correlated with the expression quantity of coxsackie virus and adenovirus receptor (CAR) in bladder cancer cells surface, which expanded the application of viral therapy in the treatment of bladder cancer
Summary
Replicative oncolytic adenoviruses (CRAds) display significant anti-tumor effects. The traditional adenovirus of serotype 5 (Ad5) entering cancer cells via coxsackie virus and adenovirus receptor (CAR) can’t be utilized for bladder cancer with low expression of CAR, which limits the application of Ad5. Bladder cancer is the most common urinary tract malignant tumor [1]. The traditional treatments for bladder cancer are radical cystectomy, radiation and chemotherapy. Replicative oncolytic adenoviruses (CRAds) lyse the cancer cells, and release a large number of progeny virus to infect other surrounding cancer cells [7]. CRAds made greater progress in the field of bladder tumor treatment [8,9,10,11]. The construction and advantages in anti-tumor effects of CRAds
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
