Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer

Cells

卷:9

Rajesh Singh¹  JamesW. Lillard¹  SantoshKumar Singh¹  EdwardP. Acosta²  JenniferB. Gordetsky³  Sejong Bae⁴ 

[1] Department of Microbiology, Biochemistry and Immunology, Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA;

[2] Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;

[3] Departments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, TN 37232, USA;

[4] Division of Preventive Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35205, USA;

关键词: prostate cancer;    thymoquinone;    drug transporter;    nanoparticles;    aptamer;   

DOI  :  10.3390/cells9091976

来源: DOAJ

【 摘 要 】

An abnormality in hedgehog (Hh) signaling has been implicated in the progression of prostate cancer (PCa) to a more aggressive and therapy-resistant disease. Our assessments of human PCa tissues have shown an overexpression of the Hh pathway molecules, glioma-associated oncogene homolog 1 (GLI-1), and sonic hedgehog (SHH). The effect of the natural compound thymoquinone (TQ) in controlling the expression of Hh signaling molecules in PCa was investigated in this study. We generated planetary ball-milled nanoparticles (PBM-NPs) made with a natural polysaccharide, containing TQ, and coated with an RNA aptamer, A10, which binds to prostate-specific membrane antigen (PSMA). We prepared docetaxel-resistant C4-2B-R and LNCaP-R cells with a high expression of Hh, showing the integration of drug resistance and Hh signaling. Compared to free TQ, A10-TQ-PBM-NPs were more effective in controlling the Hh pathway. Our findings reveal an effective treatment strategy to inhibit the Hh signaling pathway, thereby suppressing PCa progression.

【 授权许可】

Unknown