Bicalutamide inhibits androgen-mediated adhesion of prostate cancer cells exposed to ionizing radiation.
BACKGROUND
Cell adhesion plays an important role in proliferation, metastasis, and tumor growth and may represent a potential vulnerability in treatment of prostate cancer patients. Bicalutamide (Casodex) has been used as an anti-androgen agent for prostate cancer patients during hormone ablation therapy. This study focuses on the effect of Bicalutamide on cell adhesion to fibronectin (FN) in prostate cancer cells.


METHODS
Androgen-dependent LNCaP prostate cancer cells were stimulated with androgen before being irradiated with doses of 0, 5, 10, or 15 Gy. Cell adhesion to fibronectin was then measured to ascertain androgen's role in integrin mediated prostate cancer cell adhesion. Flow cytometry was used to analyze surface expression of integrin subtypes in LNCaP cells.


RESULTS
LNCaP cell adhesion to FN was significantly increased by stimulation with androgen when treated with 10 or 15 Gy ionizing radiations but not at 0 or 5 Gy. This increase was inhibited by treatment with Bicalutamide. LNCaP cells exposed to high dose radiation showed an increased expression of alpha(V) and beta(1) integrins in response to androgen treatment while Bicalutamide abolished this effect.


CONCLUSIONS
Our data show that Bicalutamide inhibits the effect of androgen on cell adhesion to FN through changes of integrin subtypes in cells given high dose radiation. This suggests new molecular targets and possible treatment strategies for prostate cancer patients to improve the outcome during hormone ablation therapy and radiation therapy.
Wang
Tao
T
Department of Radiation Oncology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Alavian
Michael R
MR
Goel
Hira Lal
HL
Languino
Lucia R
LR
Fitzgerald
Thomas J
TJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000728:Androgens / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011839:Radiation, Ionizing; D014105:Tosyl Compounds / Q000494:pharmacology*
D000728:Androgens; D000813:Anilides; D000970:Antineoplastic Agents; D005353:Fibronectins; D016023:Integrins; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide