| Autor: |
Rui Zhao, Xiaowei Ma, Lijuan Bai, Xin Li, Kenza Mamouni, Yang Yang, HongYan Liu, Alira Danaher, Nicholas Cook, Omer Kucuk, Robert S. Hodges, Lajos Gera, Daqing Wu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1261-1274 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1476-5586 |
| DOI: |
10.1016/j.neo.2021.11.006 |
| Popis: |
A major challenge to the treatment of advanced prostate cancer (PCa) is the development of resistance to androgen-deprivation therapy (ADT) and chemotherapy. It is imperative to discover effective therapies to overcome drug resistance and improve clinical outcomes. We have developed a novel class of silicon-containing compounds and evaluated the anticancer activities and mechanism of action using cellular and animal models of drug-resistant PCa. Five organosilicon compounds were evaluated for their anticancer activities in the NCI-60 panel and established drug-resistant PCa cell lines. GH1504 exhibited potent in vitro cytotoxicity in a broad spectrum of human cancer cells, including PCa cells refractory to ADT and chemotherapy. Molecular studies identified several potential targets of GH1504, most notably androgen receptor (AR), AR variant 7 (AR-v7) and survivin. Mechanistically, GH1504 may promote the protein turnover of AR, AR-v7 and survivin, thereby inducing apoptosis in ADT-resistant and chemoresistant PCa cells. Animal studies demonstrated that GH1504 effectively inhibited the in vivo growth of ADT-resistant CWR22Rv1 and chemoresistant C4-2B-TaxR xenografts in subcutaneous and intraosseous models. These preclinical results indicated that GH1504 is a promising lead that can be further developed as a novel therapy for drug-resistant PCa. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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