Naftopidil, a Selective α1-Adrenoceptor Antagonist, Suppresses Human Prostate Tumor Growth by Altering Interactions between Tumor Cells and Stroma
Autor: | Kiminobu Arima, Yoshiki Sugimura, Yoichi Iwamoto, Kenichiro Ishii, Hideki Kanda, Yasuhide Hori, Hideaki Kise, Norihito Soga, Kohei Nishikawa |
---|---|
Rok vydání: | 2011 |
Předmět: |
Male
Cancer Research medicine.medical_specialty Stromal cell Blotting Western Mice Nude Apoptosis Naphthalenes Biology medicine.disease_cause Piperazines Immunoenzyme Techniques Mice Prostate cancer Internal medicine LNCaP medicine Animals Humans RNA Messenger Cells Cultured Cell Proliferation Naftopidil Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Cell growth Prostatic Neoplasms Silodosin medicine.disease Endocrinology Oncology Cancer cell Adrenergic alpha-1 Receptor Antagonists Cancer research Stromal Cells Carcinogenesis medicine.drug |
Zdroj: | Cancer Prevention Research. 4:87-96 |
ISSN: | 1940-6215 1940-6207 |
Popis: | In prostate cancer, tumor–stroma interactions play a critical role in the promotion of tumorigenesis, and thus the prevention of those interactions is a promising target to suppress tumor growth. Several studies demonstrated that alpha1-adrenoceptor (α1-AR) antagonists, therapeutic drugs for benign prostatic hyperplasia, have growth inhibitory effects on human prostate cancer (PCa) cells through induction of apoptosis or G1 cell-cycle arrest. However, their direct actions on stromal cells surrounding cancer cells have not yet been elucidated. In this study, we investigated the effects of subtype-selective α1-AR antagonists (naftopidil, tamsulosin, and silodosin) on prostate tumor growth with a focus on the role of stroma, using commercially available fibroblast cells (PrSC). Tumorigenic studies in vivo showed significant reductions in tumor growth when E9 cells (an androgen low-sensitive LNCaP subline) grafted with PrSC were treated with naftopidil. In in vitro analyses, naftopidil and silodosin showed antiproliferative effects on PCa cells regardless of androgen sensitivity and α1-AR subtype expression. In PrSC, a strong growth inhibitory effect was observed with naftopidil but not silodosin. Flow cytometric analysis revealed that naftopidil, but not silodosin, induced G1 cell-cycle arrest in both PCa cells and PrSC. In naftopidil-treated PrSC, total interleukin-6 protein was significantly reduced with increased suppression of cell proliferation. Silodosin induced weak early apoptosis only in PCa cells. These findings demonstrated that naftopidil strongly suppressed cell proliferation of stromal cells, resulting in decreased tumorigenic soluble factor, suggesting that naftopidil might be effective in preventing stromal support of tumor cells. Cancer Prev Res; 4(1); 87–96. ©2011 AACR. |
Databáze: | OpenAIRE |
Externí odkaz: |