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.
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References
Tefekli A, Tunc M. Future prospects in the diagnosis and management of localized prostate cancer .Sci World J. 2013; 347263
Tse BW, Jovanovic L, Nelson CC, de Souza P, Power CA, Russell PJ. From bench to bedside: immunotherapy for prostate cancer. Biomed Res Int. 2014;981434.
Tefekli A, Tunc M. Future prospects in the diagnosis and management of localized prostate cancer. Sci World J. 2013; 347263.
Semenas J, Allegrucci C, Boorjian SA, Mongan NP, Persson JL. Overcoming drug resistance and treating advanced prostate cancer. Curr Drug Targets. 2012;13:1308–23.
Tsao CK, Small AC, Galsky MD, Oh WK. Overcoming castration resistance in prostate cancer. Curr Opin Urol. 2012;22:167–74.
Fillat C, Maliandi MV, Mato-Berciano A, Alemany R1. Combining oncolytic virotherapy and cytotoxic therapies to fight cancer. Curr Pharm Des. 2014;20:6513–21.
Liu XY. Targeting gene-virotherapy of cancer and its prosperity. Cell Res. 2006;16:879–86.
Notani D1, Limaye AS, Kumar PP, Galande S. Phosphorylation-dependent regulation of SATB1, the higher-order chromatin organizer and global gene regulator. Methods Mol Biol. 2010;647:317–35.
Ye CS, Zhou DN, Yang QQ, Deng YF. Silencing SATB1 influences cell invasion, migration, proliferation, and drug resistance in nasopharyngeal carcinoma. Int J Clin Exp Pathol. 2014;7:914–22.
Zhang L, Cheng F, He R, Chen H, Liu Y, Sun J. Inhibition of SATB1 by shRNA suppresses the proliferation of cutaneous malignant melanoma. Cancer Biother Radiopharm. 2014;29:77–82.
Zhang H, Qu S, Li S, Wang Y, Li Y, Wang Y, et al. Silencing SATB1 inhibits proliferation of human osteosarcoma U2OS cells. Mol Cell Biochem. 2013;378:39–45.
Huang B, Zhou H, Wang X, Liu Z. Silencing SATB1 with siRNA inhibits the proliferation and invasion of small cell lung cancer cells. Cancer Cell Int. 2013;13:8.
Mao L, Yang C, Wang J, Li W, Wen R, Chen J, et al. SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion. J Transl Med. 2013;11:111.
Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T. SATB1 reprogrammes gene expression to promote breast tumor growth and metastasis. Nature. 2008;452:187–93.
Tu W, Luo M, Wang Z, Yan W, Xia Y, Deng H, et al. Upregulation of SATB1 promotes tumor growth and metastasis in liver cancer. Liver Int. 2012;32:1064–78.
Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998;94:481–90.
Li H, Zhu H, Xu CJ, Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998;94:491–501.
Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. 1996;274:373–6.
Kirn D. Oncolytic virotherapy for cancer with the adenovirus dl1520 (Onyx-015): results of phase I and II trials. Expert Opin Biol Ther. 2001;1:525–38.
Zhang ZL, Zou WG, Luo CX, Li BH, Wang JH, Sun LY, et al. An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy. Cell Res. 2003;13:481–9.
Tsukuda K1, Wiewrodt R, Molnar-Kimber K, Jovanovic VP, Amin KM. An E2F-responsive replication-selective adenovirus targeted to the defective cell cycle in cancer cells: potentantitumoral efficacy but no toxicity to normal cell. Cancer Res. 2002;62:3438–47.
Fang XF, Hou ZB, Dai XZ, Chen C, Ge J, Shen H, et al. Special AT-rich sequence-binding protein 1 promotes cell growth and metastasis in colorectal cancer. World J Gastroenterol. 2013;19:2331–9.
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This study was supported by grant from the National Natural Science Foundation of China (No. 3070099). The supporters had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Li-jun Mao and Jie Zhang contributed equally to this work.
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Mao, Lj., Zhang, J., Liu, N. et al. Oncolytic virus carrying shRNA targeting SATB1 inhibits prostate cancer growth and metastasis. Tumor Biol. 36, 9073–9081 (2015). https://doi.org/10.1007/s13277-015-3658-x
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DOI: https://doi.org/10.1007/s13277-015-3658-x