1. Folate-targeted nanoparticle delivery of androgen receptor shRNA enhances the sensitivity of hormone-independent prostate cancer to radiotherapy
- Author
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Wenchao Lu, Zhi Ying Shao, Longzhen Zhang, Hong Yao, Jia Yin Ji, Jianshe Wang, Hui Qiu, Nianli Liu, Ronald C. Chen, and Xinjun Zhang
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Radiation-Sensitizing Agents ,Cell cycle checkpoint ,medicine.medical_treatment ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Mice, Nude ,Bioengineering ,Radiation Tolerance ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,Mice ,0302 clinical medicine ,Folic Acid ,In vivo ,Internal medicine ,Cell Line, Tumor ,medicine ,Androgen Receptor Antagonists ,Animals ,Humans ,General Materials Science ,RNA, Small Interfering ,Cell growth ,business.industry ,Prostatic Neoplasms ,medicine.disease ,Xenograft Model Antitumor Assays ,Radiation therapy ,Androgen receptor ,030104 developmental biology ,Endocrinology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Nanoparticles ,business - Abstract
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro. The radiosensitizing effect of NP AR-shRNA could be validated in vivo, as NP AR-shRNA significantly suppressed tumor growth and prolonged the survival of HIPC tumor-bearing mice. Analysis at the molecular level revealed that NP AR-shRNA inhibits DNA damage repair signaling pathways. Our study supports further investigation of NP AR-shRNA for the improvement of radiotherapy efficacy in HIPC.
- Published
- 2016