TGF-beta1 reverses inhibition of COX-2 with NS398 and increases invasion in prostate cancer cells.
Bone-derived transforming growth factor (TGF)-beta1 leads to tumor growth, osteoblastic lesions and more invasion. Degradation of basement membranes caused by cyclooxygenase (COX)-2 is known as a distinctive feature of invasive cells. We investigated inhibition of COX-2 with NS398 in PC-3 and LNCaP cell lines. TGF-beta1 and dmPGE2 were added in NS398 treated or untreated cells. COX-2 did not express in PC-3, after treatment with TGF-beta1, COX-2 appeared and accompanied with enhanced invasion. COX-2 expressed in LNCaP, undetectable after addition of NS398 along with decreased invasion. Addition of TGF-beta1 reversed inhibition of NS398 in both cell lines. DmPGE2 augmented invasion in both cell lines without alteration of COX-2. These results suggest that TGF-beta1 can increase invasion and reverse inhibition of COX-2 induced by NS398. We indicate that bone-derived TGF-beta1 might contribute to clinical unsatisfied effect of NSAIDs or COX-2 specific inhibitors adjuvant therapies. Our data provide a new potential therapy for fighting against prostate cancer.
Ding
Qiang
Q
Department of Urology, First Clinical College of Harbin Medical University, Harbin, China.
Bai
Yu-Feng
YF
Wang
Yong-Quan
YQ
An
Rui-Hua
RH
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009578:Nitrobenzenes / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology* / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D015232:Dinoprostone