Combination of oncolytic adenovirus targeting SATB1 and docetaxel for the treatment of castration-resistant prostate cancer

Abstract

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.

A comparative study of the ability of recombinant oncolytic adenovirus, doxorubicin and tamoxifen to inhibit the proliferation of breast cancer cells

“…A recent study by Mao et al, 26 involving an animal model used a combination of oncolytic adenovirus ZD55‐SATB1 to target SATB1 and DTX treatment to effectively inhibit the growth of xenograft tumours; this effect was accompanied by an increase in the expression of caspase protein and a reduction in the expression of CD31. In addition, Xiao et al showed that the oncolytic adenovirus CD55‐Smad 4 effectively inhibited the proliferation of colorectal cancer cells both in vivo and in vitro, while also activating the caspase signal transduction pathway and inducing apoptosis in colorectal cancer cells 27 .…”