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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis
Li-jun Mao1,2, Jie Zhang2, Ning Liu2
1Department of Urinary Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Abstract:
Recent studies suggest that SATB1 is a promising therapeutic target for prostate cancer. To develop novel SATB1-based therapeutic agents for prostate cancer, in this study, we aimed to construct ZD55-SATB1, an oncolytic adenovirus ZD55 carrying shRNA targeting SATB1, and investigate its effects on the inhibition of prostate cancer growth and metastasis. ZD55-SATB1 was constructed and used to infect human prostate cancer cell lines DU145 and LNCaP. The inhibitory effect of ZD55-SATB1 on SATB1 expression was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The cytotoxicity of ZD55-SATB1 was detected by MTT assay. Cell invasion was detected by Matrigel invasion assay. The in vivo antitumor activities of ZD55-SATB1 were evaluated in xenograft mouse model. We found that ZD55-SATB1 selectively replicated and significantly reduced SATB1 expression in DU145 and LNCaP cells. ZD55-SATB1 effectively inhibited the viability and invasion of DU145 and LNCaP cells in vitro and inhibited prostate cancer growth and metastasis in xenograft nude mice. In conclusion, replicative oncolytic adenovirus armed with SATB1 shRNA exhibits effective antitumor effect in human prostate cancer. Our study provides the basis for the development of ZD55-SATB1 for the treatment of prostate cancer.
Insights
A novel oncolytic adenovirus, ZD55-SATB1, effectively targets SATB1 (Special AT-rich sequence-binding protein 1) to inhibit prostate cancer growth and metastasis. This therapeutic agent shows promise for treating prostate cancer.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- SATB1 (Special AT-rich sequence-binding protein 1) is identified as a potential therapeutic target for prostate cancer.
- Developing novel agents targeting SATB1 is crucial for advancing prostate cancer treatment.
Purpose of the Study:
- To construct ZD55-SATB1, an oncolytic adenovirus carrying shRNA against SATB1.
- To evaluate the efficacy of ZD55-SATB1 in inhibiting prostate cancer cell growth, viability, invasion, and metastasis.
Main Methods:
- Construction and characterization of ZD55-SATB1.
- In vitro assessment of SATB1 expression inhibition (RT-PCR, Western blot), cytotoxicity (MTT assay), and cell invasion (Matrigel assay) in prostate cancer cell lines (DU145, LNCaP).
- In vivo evaluation of antitumor activity in a prostate cancer xenograft mouse model.
Main Results:
- ZD55-SATB1 demonstrated selective replication and significant reduction of SATB1 expression in prostate cancer cells.
- In vitro studies showed ZD55-SATB1 effectively inhibited cancer cell viability and invasion.
- In vivo experiments confirmed ZD55-SATB1's ability to inhibit tumor growth and metastasis in mice.
Conclusions:
- Replicative oncolytic adenovirus ZD55-SATB1 armed with SATB1 shRNA exhibits significant antitumor effects against human prostate cancer.
- ZD55-SATB1 presents a promising therapeutic strategy for prostate cancer treatment, warranting further clinical development.
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