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Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice
Chen, Ruibao Zhao, Yunqi Huang, Yan Yang, Qiuhong Zeng, Xing Jiang, Wencong Liu, Jihong Thrasher, J. Brantley Forrest, M. Laird Li, Benyi
Chen, Ruibao
Zhao, Yunqi
Huang, Yan
Yang, Qiuhong
Zeng, Xing
Jiang, Wencong
Liu, Jihong
Thrasher, J. Brantley
Forrest, M. Laird
Li, Benyi
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Abstract
BACKGROUND: Combination of androgen ablation along with early detection and surgery has made prostate cancer highly treatable at the initial stage. However, this cancer remains the second leading cause of cancer death among American men due to castration-resistant progression, suggesting that novel therapeutic agents are urgently needed for this life-threaten condition. Phosphatidylinositol 3-kinase p110β is a major cellular signaling molecule and has been identified as a critical factor in prostate cancer progression. In a recent report, we established a nanomicelle-based strategy to deliver p110β-specific inhibitor TGX221 to prostate cancer cells by conjugating the surface of nanomicelles with a RNA aptamer against prostate membrane specific antigen (PSMA) present in all clinical prostate cancers. In this study, we tested this nanomicellar TGX221 for its in vivo anti-tumor effect in mouse xenograft models. METHODS: Prostate cancer cell lines LAPC-4, LNCaP, C4-2 and 22RV1 were used to establish subcutaneous xenograft tumors in nude mice. Paraffin sections from xenograft tumor specimens were used in immunohistochemistry assays to detect AKT phosphorylation, cell proliferation marker Ki67 and PCNA, as well as BrdU incorporation. Quantitative PCR assay was conducted to determine PSA gene expression in xenograft tumors. RESULTS: Although systemic delivery of unconjugated TGX221 significantly reduced xenograft tumor growth in nude mice compared to solvent control, the nanomicellar TGX221 conjugates completely blocked tumor growth of xenografts derived from multiple prostate cancer cell lines. Further analyses revealed that AKT phosphorylation and cell proliferation indexes were dramatically reduced in xenograft tumors received nanomicellar TGX221 compared to xenograft tumors received unconjugated TGX221 treatment. There was no noticeable side effect by gross observation or at microscopic level of organ tissue section.
CONCLUSION: These data strongly suggest that prostate cancer cell-targeted nanomicellar TGX221 is an effective anti-cancer agent for prostate cancer.
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Date
2015-05
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Wiley
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Zhao_2015.pdf
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Prostate cancer, p110β, Nanotechnology, Micelle, TGX221, Cancer therapy
Citation
Chen, R., Zhao, Y., Huang, Y., Yang, Q., Zeng, X., Jiang, W., … Li, B. (2015). Nanomicellar TGX221 blocks xenograft tumor growth of prostate cancer in nude mice. The Prostate, 75(6), 593–602. http://doi.org/10.1002/pros.22941