Background: Oncolytic viral therapy is a new strategy for tumor eradication which combines the advantages of viral therapy and gene therapy. Silencing SATB1 exhibits strong inhibitory effect on the growth of prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase its anti-tumor effect. Methods: Oncolytic adenovirus targeting SATB1 was constructed and named ZD55-SATB1. Human prostatic cancer cells DU145 and PC-3 and human prostatic stromal cells WPMY-1 were treated with ZD55-SATB1 or/and DTX. In vitro cell proliferation, migration, invasion, apoptosis were detected. In addition, PC-3 cells were injected subcutaneously into nude mice, which were treated with ZD55-SATB1 or/and DTX. Tumor growth was monitored in vivo. Results: ZD55-SATB1 combined with DTX inhibited proliferation, migration and invasion of DU145 and PC-3 cells, while promoted apoptosis of DU145 and PC-3 cells more efficiently than monotherapy. ZD55-SATB1 had no cytotoxicity on WPMY-1 cells. In animal models, the combined treatment of ZD55-SATB1+DTX and endocrine therapy effectively inhibited the growth of xenograft tumor, accompanied by increased expression of caspase-3 and caspase-8, and decrease expression of Bcl-2 and angiogenesis marker CD31 compared to other treatment groups. Conclusion: The combination of oncolytic adenovirus ZD55-SATB1 and chemotherapy provides a novel approach to effective therapy of prostate cancer.

01 Nov 2015·Tumor Biology

Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis

Article

Author: Fan, Li ; Yang, Dong-rong ; Shan, Yu-xi ; Liu, Ning ; Zhang, Jie ; Zheng, Jun-nian ; Mao, Li-jun ; Xue, Bo-xin

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.

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	CN	Second Affiliated Hospital of Soochow University	-

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